PROBLEM: Annual mass drugadministration (MDA) with safe oral anthelminthic drugs (praziquantel, ivermectin and albendazole) is the strategy for control of onchocerciasis, lymphatic filariasis (LF) and schistosomiasis. District health officers seek to integrate treatment activities in areas of overlapping disease endemicity, but they are faced with having to merge different programmatic guidelines. APPROACH: We proceeded through the three stages of integrated MDA implementation: mapping the distribution of the three diseases at district level; tailoring district training and logistics based on the results of the mapping exercises; and implementing community-based annual health education and mass treatment where appropriate. During the process we identified the "know-do" gaps in the MDA guidelines for each disease that prevented successful integration of these programmes. LOCAL SETTING: An integrated programme launched in 1999 in Plateau and Nasarawa States in central Nigeria, where all three diseases were known to occur. RELEVANT CHANGES: Current guidelines allowed onchocerciasis and LF activities to be integrated, resulting in rapid mapping throughout the two states, and states-wide provision of over 9.3 million combined ivermectin-albendazole treatments for the two diseases between 2000 and 2004. In contrast, schistosomiasis activities could not be effectively integrated because of the more restrictive guidelines, resulting in less than half of the two states being mapped, and delivery of only 701,419 praziquantel treatments for schistosomiasis since 1999. LESSONS LEARNED: Integration of schistosomiasis into other MDA programmes would be helped by amended guidelines leading to simpler mapping, more liberal use of praziquantel and the ability to administer praziquantel simultaneously with ivermectin and albendazole. PMID:16917658

Introduction Schistosomiasis is one of the neglected tropical diseases targeted for elimination in Uganda through the Mass DrugAdministration (MDA) programme. Praziquantel has been distributed using community resource persons in fixed sites and house-to-house visits; however the uptake is still below target coverage. In 2011/2012 MDA exercise, uptake stood at 50% yet WHO target coverage is 75% at community level. We assessed the uptake of MDA and the associated factors in Koome Islands, Central Uganda. Methods In March 2013, we conducted a mixed methods cross sectional study in 15 randomly selected villages. We interviewed a total of 615 respondents aged 18 years and above using semi structured questionnaires and five key informants were also purposively selected. Univariate and multivariate analysis was done. MDA uptake was defined as self reported swallowing of praziquantel during the last (2012) MDA campaign. We conducted key informant interviews with Ministry of Health, district health personnel and community health workers. Results Self reported uptake of praziquantel was 44.7% (275/615), 95% confidence interval (CI) 40.8–48.7%. Of the 275 community members who said they had swallowed praziquantel, 142 (51.6%) reported that they had developed side effects. Uptake of MDA was more likely if the respondent was knowledgeable about schistosomiasis transmission and prevention (adjusted odds ratio [AOR] 1.85, 95% CI 1.22–2.81) and reported to have received health education from the health personnel (AOR 5.95, 95% CI 3.67–9.65). Service delivery challenges such as drug shortages and community health worker attrition also influenced MDA in Koome Islands. Conclusions Uptake of MDA for schistosomiasis control in Koome was sub optimal. Lack of knowledge about schistosomiasis transmission and prevention, inadequate health education and drug shortages are some of the major factors associated with low uptake. These could be addressed through routine health education

The impact of control and elimination programmes by mass drugadministration (MDA) targeting onchocerciasis and lymphatic filariasis (LF) in sub-Saharan Africa over the last two decades has resulted in significantly reduced prevalence and intensity of infection, with some areas interrupting transmission. However, given that these infections are often co-endemic and the drugs (either ivermectin alone or combined with albendazole) also impact on soil transmitted helminths (STH), the importance of this, in terms of reaching the global goals has not been assessed. The additional problem posed by Loa loa, where ivermectin cannot be safely administered due to the risk of serious adverse events compounds this situation and has left populations drug naïve and an alternative strategy to eliminate LF is yet to be initiated at scale. Here, we present a series of operational research questions, which must be addressed if the effectiveness of integrated control of filarial and helminth infections is to be understood for the endgame. This is particularly important in the diverse and dynamic epidemiological landscape, which has emerged as a result of the long-term large-scale mass drugadministration (or not). There is a need for a more holistic approach to address these questions. Different programmes should examine this increased complexity, given that MDA has multiple impacts, drugs are given over different periods, and programmes have different individual targets. PMID:25128408

India's mass drugadministration (MDA) programme to eliminate lymphatic filariasis (PELF) covers all 250 endemic districts, but compliance with treatment is not adequate for the programme to succeed in eradicating this neglected tropical disease. The objective of our study was to systematically review published studies on the coverage of and compliance with MDA under the PELF in India. We searched several databases-PubMed/Medline, Google Scholar, CINAHL/EBSCO, Web of Knowledge (including Web of Science) and OVID-and by applying selection criteria identified a total of 36 papers to include in the review. Overall MDA coverage rates varied between 48.8% and 98.8%, while compliance rates ranged from 20.8% to 93.7%. The coverage-compliance gap is large in many MDA programmes. The effective level of compliance, ≥65%, was reported in only 10 of a total of 31 MDAs (5 of 20 MDAs in rural areas and 2 of 12 MDAs in urban areas). The review has identified a gap between coverage and compliance, and potentially correctable causes of this gap. These causes need to be addressed if the Indian programme is to advance towards elimination of lymphatic filariasis. PMID:24728444

Background Mass drugadministration (MDA), defined as the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, has been a historic component of many malaria control and elimination programmes, but is not currently recommended. With renewed interest in MDA and its role in malaria elimination, this review aims to summarize the findings from existing research studies and program experiences of MDA strategies for reducing malaria burden and transmission. Objectives To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated adverse events. Search methods We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings. Selection criteria Cluster-randomized trials and non-randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after studies comparing post-MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub-populations (for example, pregnant women, children or infants) were excluded. Data collection and analysis Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach. Main results Two cluster-randomized trials, eight non-randomized controlled studies and 22 uncontrolled before-and-after studies are included in this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were

This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

The Drug Enforcement Administration (DEA), as part of its efforts to control the abuse and misuse of controlled substances and chemicals used in producing some over-the-counter drugs, maintains databases of individuals registered to handle these substances. These databases are av...

The Orphan Drug Act has become a staple of food and drug law in the US. The experience with the US programme continues to serve as a useful reference point as interest in orphan drug incentive programmes expands globally. This article first reviews details of the legislation and orphan drug regulations, and then provides a 13-year overview (1983-1995) of orphan drug activity in the US, including descriptive data on the designated and approved orphan drugs, their indications and sponsors. In light of a recent challenge to the Food and DrugAdministration's (FDA's) authority under the Act, we also examine the interplay between the exclusivity provision of the Act and the orphan drug regulations that define when 2 drugs will be considered the 'same' for the purposes of the Act. A recent court decision affirming the FDA's interpretation of the clinical superiority provisions of the regulations suggests that orphan exclusivity may be less predictable and less certain than it has been in the past. Finally, we consider the usefulness to orphan drug sponsors of other initiatives such as FDA's early access and fast-track approval programmes, and the extent to which the FDA's discretion to waive, defer and reduce prescription drug user fees has worked to the benefit of orphan drug sponsors. Over the 13-year analysis period, the FDA granted 631 orphan designations involving 450 different drugs, for which 121 FDA marketing approvals have been granted. Those with both treatment investigational drug designation and fast-track approval status appeared to benefit substantially from shorter development times. The indications targeted by the orphan drugs fall into 8 categories, with 40% of all orphan indications involving cancer and genetic diseases. Evident in the latter part of the analysis period is the increasing share of orphan activity attributable to biotechnology firms. Even though the Prescription Drug User Fee Act of 1992 did not recognise orphan status for the purpose of

These guidelines were developed to assist administrators, teachers, and other staff members of the Los Angeles Public Schools in the formulation of an effective program designed to alleviate drug abuse. Staff responsibilities are spelled out. Specific attention is directed to the problems of drug abuse, drug possession and drug selling. The…

Because of easiness and accessibility, the oral route of administration is usually the route of choice for medication delivery, as long as the oral drug form is available and the patients' circumstances allow it.In patients admitted to the intensive care unit this route is frequently altered. This provokes difficulties in swallowing and consequently an enteral feeding catheter must be inserted to supply the patient's nutritional requirements. This catheter is also used for the drugadministration, which necessitates opening capsules or crushing pills before dilution. When added to drug-nutrient interactions, this process alters the drug's properties and modifies its pharmacokinetic profile, its pharmacological effect and the intensity of side effects. It can also provoke catheter obstruction. The aim of this study was to establish guidelines for drugadministration through enteral feeding catheters. We provide a thorough review of the literature, describe oral drug forms, present a protocol for correct drugadministration and provide a guide to the most commonly used drugs in our unit. For each of these drugs we include recommendations on administration and possible alternatives. PMID:11459545

... International, Inc. By Notice dated May 14, 2013, and published in the Federal Register on May 22, 2013, 78 FR... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug... renewal to the Drug Enforcement Administration (DEA) to be registered as a bulk manufacturer of...

While clinical disease caused by drug-sensitive Mycobacterium tuberculosis (MTB) can usually be treated successfully, clinical disease caused by drug-insensitive MTB is associated with a poorer prognosis. In December 2012, a new drug, bedaquiline, was approved by the US Food and DrugAdministration. This article documents the process whereby the National Department of Health, Right to Care and Médecins Sans Frontières obtained access to this medication for South Africans who might benefit from subsequent implementation of the Clinical Access to Bedaquiline Programme. PMID:24897814

Recent developments in nanomedicine for the cancer therapy have enabled programmable delivery of therapeutics by exploiting the stimuli-responsive properties of nanocarriers. These therapeutic systems were designed with the relevant chemical and physical properties that respond to different triggers for enhanced anticancer efficacy, including the reduced development of drug-resistance, lower therapeutic dose, site-specific transport, and spatiotemporally controlled release. This minireview discusses the current advances in programmable nanocarriers for cancer therapy with particular emphasis on synergistic and sequential drug delivery systems.

Public health measures are still the most important factor in improving Third World health. However, medicines have an important part to play, and it is now generally agreed that for the very poor populations medicines should be restricted to those on an 'essential drugs list' and should be made available as cheaply as possible. A major problem arises, however, in trying to stop these very cheap supplies 'leaking' back into the private sector, and being sold to the public at high prices. This is particularly true as many countries have a large rich urban elite as well as a much larger poor rural population. It is also important to recognise that research into Third World diseases must be financed by profits on the sale of medicines in advanced countries. A 'cheap drug' policy in rich countries can be very harmful to the long-term health even of the less developed countries. PMID:3686096

Background: This paper is the result of our interest in preventing adaptation problems (delinquency, academic failure and absenteeism at school, drug use, etc.) in young children and adolescents at risk, as well as the need to develop effective programmes adapted to the population in the Balearic Islands (Spain). Purpose: The objective of this…

Assessment of the efficacy of anthelminthic treatment in public health is a broad concept, which goes beyond parasitological methods and should be clearly defined according to several indicators of morbidity. Several factors may influence the efficacy of anthelminthic drugs. The quality of drug is an issue of great importance, especially when produced locally as a generic product and used in large-scale chemotherapy-based control programmes. Other factors include the drug-patient interaction, the host-parasite relationship, the diagnostic method used, genetic variations between parasite strains and induced drug resistance. Veterinary scientists have warned that drug resistance can be selected through frequent mass treatment of sheep and goats and have developed a body of knowledge on evaluation of efficacy and detection of resistance in nematodes of veterinary importance. In soil-transmitted nematodes infections of humans, the egg reduction rate (ERR), the egg hatch assay (EHA) and novel molecular biological techniques may be used to monitor drug efficacy in helminth control programmes and to detect early occurrence of resistance. Evidence of reduced drug efficacy of some anthelminthics has been suggested by recent studies and strategies to prevent or delay the emergence of drug resistance in human soil-transmitted nematodes. PMID:12745140

The trouble with some tasks and procedures in nursing is that you get too used to them, and errors inevitably set in. No other area is as vulnerable to this as drugadministration. A recent report from the National Patient Safety Agency highlighted that dozens of patients are killed every year by drug errors. In 2007, the watchdog received reports from NHS staff of 86 000 mistakes in prescribing or administering medicines, compared with 36 335 errors in 2005. In England and Wales, in 96% of cases the incidents caused low or no harm, but 37 patients died during 2007, and another 63 suffered severe harm. PMID:19966750

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Food and DrugAdministration manuals. 20.107... Administration manuals. (a) Food and DrugAdministrationadministrative staff manuals and instructions that affect a member of the public are available for public disclosure. An index of all such manuals...

Bioadhesion (and mucoadhesion) is the process whereby synthetic and natural macromolecules adhere to mucosal surfaces in the body. If these materials are then incorporated into pharmaceutical formulations, drug absorption by mucosal cells may be enhanced or the drug released at the site for an extended period of time. For synthetic polymers, such as the chitosans, carbopols and carbomers, the mechanism of bio/mucoadhesion is the result of a number of different physicochemical interactions. Biological bio/mucoadhesives, such as plant lectins, show specific interactions with cell surfaces and mucin and are seen as the 'second generation' bioadhesives. Bioadhesive systems for drugadministration via the buccal and nasal cavities are nearing the market; in the case of nasal bioadhesion, bioadhesive microparticles are used. A bioadhesive formulation for drugadministration to the vagina is in use. The gastrointestinal tract is proving a more difficult site because of the rapid turnover of mucus, and relatively constant transit time, but intensive research is in progress. Micro- and nano-particles, coated with either bio/mucoadhesive polymers or specific biological bioadhesives, are showing some promise, but will require considerable research and development before reaching the market. PMID:11286325

Chronic pain may recur after initial response to strong opioids in both patients with cancer and patients without cancer or therapy may be complicated by intolerable side effects. When minimally invasive interventional pain management techniques also fail to provide satisfactory pain relief, continuous intrathecal analgesic administration may be considered. Only 3 products have been officially approved for long-term intrathecal administration: morphine, baclofen, and ziconotide. The efficacy of intrathecal ziconotide for the management of patients with severe chronic refractory noncancer pain was illustrated in 3 placebo-controlled trials. A randomized study showed this treatment option to be effective over a short follow-up period for patients with pain due to cancer or AIDS. The efficacy of intrathecal opioid administration for the management of chronic noncancer pain is mainly derived from prospective and retrospective noncontrolled trials. The effect of intrathecal morphine administration in patients with pain due to cancer was compared with oral or transdermal treatment in a randomized controlled trial, which found better pain control and fewer side effects with intrathecal opioids. Other evidence is derived from cohort studies. Side effects of chronic intrathecal therapy may either be technical (catheter or pump malfunction) or biological (infection). The most troublesome complication is, however, the possibility of granuloma formation at the catheter tip that may induce neurological damage. Given limited studies, the evidence for intrathecal drugadministration in patients suffering from cancer-related pain is more compelling than that of chronic noncancer pain. PMID:24118774

Recent advancement in microfabrication has enabled the implementation of implantable drug delivery devices with precise drugadministration and fast release rates at specific locations. This article presents a membrane-based drug delivery device, which can be electrically stimulated to release drugs on demand with a fast release rate. Hydrogels with ionic model drugs are sealed in a cylindrical reservoir with a separation membrane. Electrokinetic forces are then utilized to drive ionic drug molecules from the hydrogels into surrounding bulk solutions. The drug release profiles of a model drug show that release rates from the device can be electrically controlled by adjusting the stimulated voltage. When a square voltage wave is applied, the device can be quickly switched between on and off to achieve pulsatile release. The drug dose released is then determined by the duration and amplitude of the applied voltages. In addition, successive on/off cycles can be programmed in the voltage waveforms to generate consistent and repeatable drug release pulses for on-demand drug delivery. PMID:25825612

The recent article by Mohammed et al. demonstrates an impressive effect of ivermectin mass drugadministration for lymphatic filariasis on the burden of scabies. Partnering scabies research within the evaluation and monitoring of Neglected Tropical Disease programmes could potentially increase our understanding of the epidemiology and control of scabies and its important bacterial complications. PMID:23594459

Falciparum malaria is a major cause of death and illness in tropical countries, particularly in childhood. In endemic countries, a significant proportion of the community is infected with malaria asymptomatically. One promising way to eliminate malaria is to give the entire population malaria treatment. This is called mass drugadministration (MDA) and it raises a number of ethical issues, as possible long-term benefits are uncertain. The effectiveness of MDA is critically dependent on level of participation, so the promised benefits to the community can be annulled by non-participation of a small number of individuals. These potential benefits range a wide spectrum, from the permanent elimination of malaria (success) to a transient reduction in the prevalence of infection and the incidence of illness (failure). The drawbacks of MDA are: inconvenience, potential toxicity, loss of confidence in the elimination campaign, possible drug resistance (though highly unlikely), and the potential for a rebound of malaria illness (if immunity is lost and malaria is reintroduced later). Other ethical issues are related to balancing individual and public health interests, and potentially limiting individual autonomy by making MDA compulsory. PMID:27481834

... HUMAN SERVICES Food and DrugAdministration 2011 Parenteral Drug Association/Food and Drug... AGENCY: Food and DrugAdministration, HHS. ACTION: Notice of public conference. The Food and Drug.... Written requests are to be sent to Division of Freedom of Information (ELEM-1029), Food and...

Recent debates about deworming school-aged children in East Africa have been described as the 'Worm Wars'. The stakes are high. Deworming has become one of the top priorities in the fight against infectious diseases. Staff at the World Health Organization, the Gates Foundation and the World Bank (among other institutions) have endorsed the approach, and school-based treatments are a key component of large-scale mass drugadministrationprogrammes. Drawing on field research in Uganda and Tanzania, and engaging with both biological and social evidence, this article shows that assertions about the effects of school-based deworming are over-optimistic. The results of a much-cited study on deworming Kenyan school children, which has been used to promote the intervention, are flawed, and a systematic review of randomized controlled trials demonstrates that deworming is unlikely to improve overall public health. Also, confusions arise by applying the term deworming to a variety of very different helminth infections and to different treatment regimes, while local-level research in schools reveals that drug coverage usually falls below target levels. In most places where data exist, infection levels remain disappointingly high. Without indefinite free deworming, any declines in endemicity are likely to be reversed. Moreover, there are social problems arising from mass drugadministration that have generally been ignored. Notably, there are serious ethical and practical issues arising from the widespread practice of giving tablets to children without actively consulting parents. There is no doubt that curative therapy for children infected with debilitating parasitic infections is appropriate, but overly positive evaluations of indiscriminate deworming are counter-productive. PMID:27428063

... Under the Federal Food, Drug, and Cosmetic Act AGENCY: Food and DrugAdministration, HHS. ACTION: Notice...) Requests for Information Under the Federal Food, Drug, and Cosmetic Act.'' This draft guidance is not final...) Requests for Information Under the Federal Food, Drug, and Cosmetic Act'' to the Division of...

Background In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drugadministration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interruption within reasonable time. The present study aimed to identify predictors and barriers to individual drug uptake during MDA implementation by the National LF Elimination Programme in Tanzania. Methods A questionnaire based cross sectional household survey was carried out in two rural and two urban districts in Lindi and Morogoro regions shortly after the 2011 MDA. 3279 adults (≥15 years) were interviewed about personal characteristics, socio-economic status, MDA drug uptake among themselves and their children, reasons for taking/not taking drugs, and participation in previous MDA activities for LF control. Findings The overall drug uptake rate was 55.1% (range of 44.5–75.6% between districts). There was no overall major difference between children (54.8%) and adults (55.2%) or between females (54.9%) and males (55.8%), but the role of these and other predictors varied to some extent between study sites. Major overall predictors of drug uptake among the interviewed adults were increasing age and history of previous drug uptake. Being absent from home during drug distribution was the main reason for not taking the drugs (50.2%) followed by clinical contraindications to treatment (10.8%), missing household visits of drug distributors (10.6%), and households not being informed about the distribution (9.0%). Conclusion Drug uptake relied more on easily modifiable provider-related factors than on individual perceptions and practices in the target population. Limited investments in appropriate timing, dissemination of accurate timing information to recipients and motivation of drug distributors to visit all households (repeatedly when residents are absent) are likely to have

Social learning theories of drug abuse propose that individuals imitate drug use behaviors modeled by social peers, and that these behaviors are selectively reinforced and/or punished depending on group norms. Historically, animal models of social influence have focused on distal factors (i.e., those factors outside the drug-taking context) in drug self-administration studies. Recently, several investigators have developed novel models, or significantly modified existing models, to examine the role of proximal factors (i.e., those factors that are immediately present at the time of drug taking) on measures of drug self-administration. Studies using these newer models have revealed several important conclusions regarding the effects of social learning on drug abuse: 1) the presence of a social partner influences drug self-administration, 2) the behavior of a social partner determines whether social contact will increase or decrease drug intake, and 3) social partners can model and imitate specific patterns of drug self-administration. These findings are congruent with those obtained in the human laboratory, providing support for the cross-species generality and validity of these preclinical models. This mini-review describes in detail some of the preclinical animal models used to study social contact and drug self-administration to guide future research on social learning and drug abuse. PMID:26159089

The rising incidence of drug abuse among youths in Nigeria is a source of concern for health educators. This study was carried out on primary six pupils to determine the effect of a Multiple Intelligences Teaching Approach Drug Education Programme (MITA-DEP) on pupils' acquisition of drug refusal skills. A programme of drug education based on the Multiple Intelligences Teaching Approach (MITA) was developed. An experimental group was taught using this programme while a control group was taught using the same programme but developed based on the Traditional Teaching Approach. Pupils taught with the MITA acquired more drug refusal skills than those taught with the Traditional Teaching Approach. Urban pupils taught with the MITA acquired more skills than rural pupils. There was no statistically significant difference in the mean refusal skills of male and female pupils taught with the MITA. PMID:25288586

Once a drug has been approved by the United States Food and DrugAdministration and is on the market, the Food and DrugAdministration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and DrugAdministration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug. PMID:26962391

Once a drug has been approved by the United States Food and DrugAdministration and is on the market, the Food and DrugAdministration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and DrugAdministration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug. PMID:26962391

This guide to drugs on the college campus provides accurate information to help administrators and other college officials understand and cope with the use of drugs by college students. The problem is defined, and facts about drugs, and the implications and issues occasioned by their use, are presented. Information is also offered in the following…

Background Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drugadministration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk. Methodology/Principal Findings To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications. Conclusions/Significance MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones. PMID:17989784

The aim of the study was to determine the effectiveness of a feedback intervention on adherence to disinfection procedures during intravenous medication preparation and administration. We found that full adherence to the protocols significantly improved from 7.3% to 21.5% (P administration. However, disinfection practices still need improvement. PMID:26899528

... listed in 21 CFR 1308.12 in locked compartments under proper temperature controls, permit only authorized... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system...

... listed in 21 CFR 1308.12 in locked compartments under proper temperature controls, permit only authorized... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system...

... listed in 21 CFR 1308.12 in locked compartments under proper temperature controls, permit only authorized... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system...

... listed in 21 CFR 1308.12 in locked compartments under proper temperature controls, permit only authorized... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system...

... listed in 21 CFR 1308.12 in locked compartments under proper temperature controls, permit only authorized... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Administration of drugs... of drugs. The program management must assist with the management of medication and have a system...

Aim: It was aimed to determine the difficulties experienced by pediatric nurses working in the wards of a university hospital during preparation and administration of drugs and to determine solution recommendations. Material and Methods: One hundred and eight nurses who accepted to participate in the study constituted the sample of the study. Open-ended questions were asked in order to obtain detailed information about the attitudes and views of the participants and face to face interview was used. The problems experienced during preparation and administration of drugs were collected using the data collection form prepared by the investigators. Institution approval, ethics committee approval (HEK12/193) and written informed consent from the nurses who wished to participate in the study were obtained to conduct the study. The data obtained were expressed as figures and percentages. Results: The most commonly reported problems in preparation of drugs included incomplete dissolution of tablets or non-homogeneous distribution in fluids (54.6%) and difficulty in breaking tablets in appropriate doses (45.3%). The most commonly reported problem experienced during administration of drugs was rejection of drugs which tasted bad by babies/children or spitting out the drug (75.9%). In our study, the nurses also mentioned the problems related with drugadministration equipment. These problems included fear of injectors (25.9%), escape of the drugs into the respiratory way (15.7%) and lack of appropriate equipment for administering the drugs (7.4%). Conclusions: In our study, it was found that all nurses experienced difficulty in preparing and administering drugs. The problems experienced by the nurses and solution recommendations for these problems were reported to the hospital administration. PMID:26078668

...The Food and DrugAdministration (FDA) is announcing a meeting for patients, caregivers, patient advocates, as well as patient advocate and health professional groups, to provide a primer on drug product development and explore patient involvement in drug development. The meeting will serve as a forum for FDA's patient stakeholders and the general public, including health professionals,......

...The Food and DrugAdministration (FDA), in cosponsorship with the Drug Information Association (DIA), is announcing a public conference entitled ``Seventh Annual DIA/FDA Statistics Forum--2013.'' The purpose of the conference is to discuss relevant statistical issues associated with the development and review of therapeutic drugs and biologics. This meeting is intended to be an open forum for......

This paper provides an overview of current formulation approaches to mitigate toxicity of orally administrateddrugs. The formulation approaches are characterized by their intended impact on a drug's pharmacokinetic parameters, pharmacological properties or metabolic pathways. Regulatory opportunities and constraints with focus on U.S. regulations in optimizing a drug's safety or efficacy profile are reviewed. The following formulation approaches are described: (i) pharmacokinetic-modulating and (ii) pharmacodynamic-modulating. In the pharmacokinetic-modulating approach, the pharmacokinetic profile of drug release is modified by, for example, a reduction in peak drug plasma concentration while preserving or improving AUC, thereby potentially reducing toxic effects that may be related to C(max). In the pharmacodynamic-modulating approach, the drug is co-dosed with pharmacologically active or nonpharmacologically active agent or agents intended for mitigation of the drug's toxicity. The pharmacodynamic-modulating approach requires information on the specificity of drug interactions with other compounds and also on metabolic pathways. Examples demonstrating successful formulation work in reducing drug toxicity are provided. The in-depth knowledge of the drug's PK and PD properties combined with a greater understanding of the biology of diseases are necessary for successful drug product formulation leading to optimized in vivo exposure and minimized toxicity. PMID:23317423

Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and continued use despite negative consequences. Behavioral impulsivity is a strong predictor of the initiation and maintenance of drug addiction. Preclinical data suggest that heroin may exacerbate impulsive characteristics in an individual but this has yet to be assessed in clinical samples. The current secondary data analysis sought to investigate the effects of heroin on impulsivity along with the effects of exposure to drug cues. Using the current data set, we also tentatively assessed the etiological relationship between impulsivity and heroin abuse. Sixteen heroin-dependent participants were recruited to complete Immediate Memory Task/Delayed Memory Task (IMT/DMT) and GoStop tasks following repeated heroin administration, following acute heroin administration, and following a drug cue exposure session. Four preceding days of active heroin availability, compared to four preceding days of placebo drug availability, increased impulsivity assessed using the IMT and DMT. Presentation of drug cues similarly acted to increase impulsivity assessments on all three tasks. It also appears that heavier users were more susceptible to the influence of drug cues on impulsivity. The present study represents a step toward a more comprehensive understanding of the interaction between opioid abuse and impulsivity. A better understanding of these factors could provide critical insight into the maintenance of heroin use and relapse. PMID:27062912

The concepts of behavioral economics have proven useful for understanding the environmental control of overall levels of responding for a variety of commodities, including reinforcement by drug self-administration. These general concepts are summarized for application to the analysis of drug-reinforced behavior and proposed as the basis for future applications. This behavioral agenda includes the assessment of abuse liability, the assay of drug-reinforcer interactions, the design of drug abuse interventions, and the formulation of drug abuse public policy. These separate domains of investigation are described as part of an overall strategy for designing model projects to control drug use and testing public policy initiatives. PMID:1955823

In this article, the processing of investigational and new drug applications is described and the standard and expedited review processes are examined. The efforts of the US Food and DrugAdministration to ensure greater agency transparency and fiscal responsibility and intensify oversight during the drug development and approval process are reviewed. Often attributed to a decrease in the number of uninsured adults, both the increase in prescription drug sales and the high costs associated with bringing a new drug to market highlight the necessity for a streamlined and cost-effective process to deliver these drugs safely and effectively. PMID:26897420

Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmabledrug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmabledrug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug

Objectives: To examine the relationship between a belief about Food and DrugAdministration (FDA) safety evaluation of cigarettes and smoking risk perceptions. Methods: A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Results: Smokers reporting that the FDA does not evaluate cigarettes for…

... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration and Process Analytical Technology for Pharma Manufacturing: Food and DrugAdministration--Partnering With Industry; Public Conference AGENCY: Food and DrugAdministration,...

In order to achieve their desired aims, evidence-based, theory-driven drug education programmes need to be implemented as intended. Measurement of 'fidelity of implementation' is now included increasingly as part of programme evaluation, although measures and methods are sometimes limited. A more sophisticated approach to assessing implementation fidelity, based on Dane & Schneider's (1998) five dimensions, was used to examine the classroom curriculum element of the Blueprint programme. Blueprint was the largest and most rigorous evaluation of a multi-component drug prevention programme to date in the United Kingdom. Lessons were, overall, delivered with reasonable fidelity, although teachers did not always understand the thinking behind particular activities, suggesting that training needs to focus not only on content and methods but why particular approaches are important. Different dimensions of fidelity could conflict with one another: under pressure of time, generic elements and processes designed to reflect on learning were sometimes sacrificed in order that core drug education activities could be completed. Future drug education curricula need to build in more flexibility for discussion without compromising core evidence-based elements. Even with substantial training and support, individual variations in delivery were found, although few differences were found between teachers with prior expertise and teachers new to drug education. The methods and measures applied in the Blueprint study all represent attempts to improve on previous measures in terms of both reliability and sensitivity. In this respect the Blueprint study represents a valuable contribution to the science of implementation fidelity. PMID:17943526

The implantation of a drug (opioid) infusion system catheter at the level of the cisterna magna, connected to an implanted programmable pump (Synchromed pump, 8611-H, Medtronic, Minneapolis, MN) is the procedure we use most commonly for the treatment of craniofacial and upper cervical pain. Our implantation technique, which we consider simple and easy to perform, is discussed in this article. Our results have been extremely encouraging, without untoward effects occurring. Adverse effects are prevented by the close proximity of the catheter tip to the pain receptors. PMID:22150811

...The Food and DrugAdministration (FDA) is providing notice of a memorandum of understanding (MOU) between FDA and Drugs.Com. The purpose of the MOU is to extend the reach of FDA Consumer Health Information and to provide consumers with better information and timely content concerning public health and safety topics, including alerts of emerging safety issues and product...

Prior to 1994, most Delhi hospitals and dispensaries experienced constant shortages of essential medicines. There was erratic prescribing of expensive branded products, frequent complaints about poor drug quality and low patient satisfaction. Delhi took the lead in developing a comprehensive Drug Policy in 1994 and was the only Indian state to have such a comprehensive policy. The policy's main objective is to improve the availability and accessibility of quality essential drugs for all those in need. The Delhi Society for the Promotion of Rational Use of Drugs (DSPRUD), a non-governmental organization, worked in close collaboration with the Delhi Government and with universities to implement various components of the policy. The first Essential Drugs List (EDL) was developed, a centralized pooled procurement system was set up and activities promoting rational use of drugs were initiated. In 1997, the Delhi Programme was designated the INDIA-WHO Essential DrugsProgramme by the World Health Organization. The EDL was developed by a committee consisting of a multidisciplinary group of experts using balanced criteria of efficacy, safety, suitability and cost. The first list contained 250 drugs for hospitals and 100 drugs for dispensaries; the list is revised every 2 years. The pooled procurement system, including the rigorous selection of suppliers with a minimum annual threshold turnover and the introduction of Good Manufacturing Practice inspections, resulted in the supply of good quality drugs and in holding down the procurement costs of many drugs. Bulk purchasing of carefully selected essential drugs was estimated to save nearly 30% of the annual drugs bill for the Government of Delhi, savings which were mobilized for procuring more drugs, which in turn improved availability of drugs (more than 80%) at health facilities. Further, training programmes for prescribers led to a positive change in prescribing behaviour, with more than 80% of prescriptions being from

... Administration: Food and DrugAdministration Clinical Trial Requirements, Regulations, Compliance, and Good... workshop regarding FDA's clinical trial requirements is designed to aid the clinical research professional... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

Introduction Young people with drug and alcohol problems are likely to have poorer health and other psychosocial outcomes than other young people. Residential treatment programmes have been shown to lead to improved health and related outcomes for young people in the short term. There is very little robust research showing longer term outcomes or benefits of such programmes. This paper describes an innovative protocol to examine the longer term outcomes and experiences of young people referred to a residential life management and treatment programme in Australia designed to address alcohol and drug issues in a holistic manner. Methods and analysis This is a mixed-methods study that will retrospectively and prospectively examine young people's pathways into and out of a residential life management programme. The study involves 3 components: (1) retrospective data linkage of programme data to health and criminal justice administrative data sets, (2) prospective cohort (using existing programme baseline data and a follow-up survey) and (3) qualitative in-depth interviews with a subsample of the prospective cohort. The study will compare findings among young people who are referred and (a) stay 30 days or more in the programme (including those who go on to continuing care and those who do not); (b) start, but stay fewer than 30 days in the programme; (c) are assessed, but do not start the programme. Ethics and dissemination Ethics approval has been sought from several ethics committees including a university ethics committee, state health departments and an Aboriginal-specific ethics committee. The results of the study will be published in peer-reviewed journals, presented at research conferences, disseminated via a report for the general public and through Facebook communications. The study will inform the field more broadly about the value of different methods in evaluating programmes and examining the pathways and trajectories of vulnerable young people. PMID

This paper will review 1) experimental models of drug-seeking behavior and 2) mechanisms underlying the behavior, focusing on cocaine self-administration. After the acquisition of self-administration, vigorous lever-pressing is generally observable after the drug was replaced by saline. This lever-pressing behavior under saline infusion can be considered "drug-seeking behavior". Drug-seeking behavior is reinstated by non-contingent injection of the drug, stress exposure and presentation of drug-associated stimuli even after extinction. This is called a relapse/reinstatement model. Electrophysiological studies showed that the majority of accumbal neurons is tonically inhibited during cocaine self-administration and exhibited phasic increases in firing time-locked to cocaine self-infusion, which might represent the craving state or drive animals to drug-seeking behavior. Voltammetry and microdialysis studies indicated that the timing of drug-seeking responses can be predicted from fluctuations in accumbal extracellular dopamine concentration. Whereas dopamine D2-like agonists reinstated extinguished cocaine-seeking behavior, D1-like agonists prevented the relapse in cocaine-seeking behavior induced by cocaine itself. Given that an AMPA receptor antagonist, but not dopamine antagonist, prevented cocaine-seeking behavior induced by cocaine, glutamate transmission in the nucleus accumbens is thought to be important for expression of craving or drug-seeking behavior. PMID:11233296

Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmabledrug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release. PMID:26554664

Lymphatic filariasis has been targeted for elimination by 2020, and a threshold of 65% coverage of mass drugadministration (MDA) has been adopted by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A recent review by Babu and Babu of 36 studies of MDA for lymphatic filariasis in India found that coverage, defined as receipt of tablets, ranged from 48.8 to 98.8%, while compliance, defined as actual ingestion of tablets, was 22% lower on average. Moreover, the denominator for these coverage figures is the eligible, rather than total, population. By contrast, the 65% threshold, in the original modelling study, refers to ingestion of tablets in the total population. This corresponds to GPELF's use of 'epidemiological drug coverage' as a trigger for the Transmission Assessment Surveys (TAS), which indicate whether to proceed to post-MDA surveillance. The existence of less strict definitions of 'coverage' should not lead to premature TAS that could impair MDA's sustainability. PMID:25575555

The administration of drugs to neonates poses significant challenges. The aim of this review was to provide insight into some of these challenges and resolutions that may be encountered with several of the most commonly used routes of administration and dosage forms in neonatal care, including oral, parenteral, transdermal, intrapulmonary, and rectal. Important considerations include fluctuations in stomach pH hours to years after birth, the logistics of setting up an intravenous infusion, the need for reduced particle size for aerosol delivery to the developing neonatal lung, and variation in perirectal venous drainage. Additionally, some of the recently developed technologies for use in neonatal care are described. While the understanding of neonatal drug delivery has advanced over the past several decades, there is still a deficiency of technologies and formulations developed specifically for this population. PMID:26245673

The Food and DrugAdministration regulates the sale and distribution of laboratory devices under a statutory and regulatory framework that is unfamiliar to most clinical laboratory scientists. In this article we briefly describe the criteria that are used to classify and review in vitro diagnostic devices. We discuss the similarities and differences between devices that are not subject to premarket review, and those that are required to undergo either a premarket application or premarket notification [510(k)] pathway. We then discuss the methods that the Food and DrugAdministration uses to assess the performance of in vitro diagnostic devices in the marketplace as a component of the total life cycle approach to medical device regulation. PMID:15681468

In this paper the model predictive control (MPC) technology is used for tackling the optimal drugadministration problem. The important advantage of MPC compared to other control technologies is that it explicitly takes into account the constraints of the system. In particular, for drug treatments of living organisms, MPC can guarantee satisfaction of the minimum toxic concentration (MTC) constraints. A whole-body physiologically-based pharmacokinetic (PBPK) model serves as the dynamic prediction model of the system after it is formulated as a discrete-time state-space model. Only plasma measurements are assumed to be measured on-line. The rest of the states (drug concentrations in other organs and tissues) are estimated in real time by designing an artificial observer. The complete system (observer and MPC controller) is able to drive the drug concentration to the desired levels at the organs of interest, while satisfying the imposed constraints, even in the presence of modelling errors, disturbances and noise. A case study on a PBPK model with 7 compartments, constraints on 5 tissues and a variable drug concentration set-point illustrates the efficiency of the methodology in drug dosing control applications. The proposed methodology is also tested in an uncertain setting and proves successful in presence of modelling errors and inaccurate measurements. PMID:24986530

... Administration (FDA) is announcing an amendment to the notice of meeting of the Science Board to the Food and DrugAdministration. This meeting was announced in the Federal Register of January 30, 2013 (78 FR 6332... HUMAN SERVICES Food and DrugAdministration Science Board to the Food and DrugAdministration...

Drugs are introduced into the body by numerous routes such as enteral (oral, sublingual and rectum administration), parenteral (intravascular, intramuscular, subcutaneous and inhalation administration), or topical (skin and mucosal membranes). Each route has specific purposes, advantages and disadvantages. Today, the oral route remains the preferred one for different reasons such as ease and compliance by patients. Several nanoformulated drugs have been already approved by the FDA, such as Abelcet®, Doxil®, Abraxane® or Vivagel®(Starpharma) which is an anionic G4-poly(L-lysine)-type dendrimer showing potent topical vaginal microbicide activity. Numerous biochemical studies, as well as biological and pharmacological applications of both dendrimer based products (dendrimers as therapeutic compounds per se, like Vivagel®) and dendrimers as drug carriers (covalent conjugation or noncovalent encapsulation of drugs) were described. It is widely known that due to their outstanding physical and chemical properties, dendrimers afforded improvement of corresponding carried-drugs as dendrimer-drug complexes or conjugates (versus plain drug) such as biodistribution and pharmacokinetic behaviors. The purpose of this manuscript is to review the recent progresses of dendrimers as nanoscale drug delivery systems for the delivery of drugs using enteral, parenteral and topical routes. In particular, we focus our attention on the emerging and promising routes such as oral, transdermal, ocular and transmucosal routes using dendrimers as delivery systems. PMID:23415951

A growing body of evidence suggests that the drug concentration in the effect compartment of the body is the major factor regulating self-administration behavior. A novel computer-based protocol was developed to facilitate studies on mechanisms of drug addiction by determining correlations between drug levels and behavior during multiple drug injections and infusions. The core of the system is a user's program written in Medstate Notation language (Med-Associates, Inc.), which runs the self-administration session (with MED-PC software and hardware, Med-Associates, Inc.) and calculates the levels of infused and/or injected drugs in real time during the session. From the comparison of classical exponential and simple linear models of first-order kinetics, it is concluded that exponential solutions for the appropriate differential equations may be replaced with linear equations if the cycle of computation is much shorter than the shortest half-life for the drug. The choice between particular computation equations depends on assumptions about the pharmacokinetics of the particular drug: (i) one-, two- or three-compartment model, (ii) zero-, first- or second-order process of elimination, (iii) the constants of distribution and elimination half-lives of the drug are known or can be reasonably assumed, (iv) dependence of the constants on the drug level, and (v) temporal stability of all parameters during the session. This method of drug level computation can be employed not only for self-administration but also for other behavioral paradigms to advance pharmacokinetic/pharmacodynamic modeling. PMID:15878149

Most drug-drug interactions involve overlap or competition in drug metabolic pathways. However, there are medications, typically resins, whose function is to bind injurious substances such as bile acids or potassium within the digestive tract. The objective of this article is to review the functions of the stomach and the kinetics of emptying of different food forms or formulations to make recommendations on timing of medication administration in order to avoid intragastric drug interactions. Based on the profiles and kinetics of emptying of liquid nutrients and homogenized solids, a window of 3 h between administration of a resin drug and another 'target' medication would be expected to allow a median of 80% of medications with particle size <1 mm to empty from the stomach and, hence, avoid potential interaction such as binding of the 'target' medication within the stomach. PMID:26987693

This study assesses relationships between drugadministration routes and HIV serostatus, drug-use and sexual behaviors among current injecting drug users (IDUs) in Tallinn, Estonia. We recruited 350 IDUs for a cross-sectional risk behavior survey. Adjusted odds ratios (AORs) were calculated to explore injection risk behavior, sexual behavior and HIV serostatus associated with multiple route use. Focus groups explored reasons why injectors might use non-injecting routes of administration. Those reporting multiple drugadministration routes were less likely to be HIV seropositive (AOR 0.49; 95%CI 0.25-0.97), had almost twice the odds of having more than one sexual partner (AOR 1.90; 95%CI 1.01-3.60) and of reporting having sexually transmitted diseases (AOR 2.38; 95%CI 1.02-5.59). IDUs who engage in non-injecting drug use may be reducing their risk of acquiring HIV though sharing injection equipment, but if infected may be a critical group for sexual transmission of HIV to people who do not inject drugs. PMID:22116012

Professor Cass Sunstein argues that the FDA has the authority to regulate tobacco products. He considers the text of the Federal Food, Drug, and Cosmetic Act, which supports the FDA assertion, and the context of its enactment, which argues against the FDA. He resolves the tension between text and context in favor of FDA jurisdiction by turning to the emerging role of administrative agencies. In modern government, he contends, administrative agencies have become America's common law courts, with the power to adapt statutory regimes to new facts and new values when the underlying statute is ambiguous. Professor Sunstein's Article, like the other pieces in this volume, was written after the United States District Court for the Middle District of North Carolina decided Coyne Beahm v. FDA, but before a three judge panel of the United States Court of Appeals for the Fourth Circuit reversed that decision in Brown & Williamson Tobacco Corp. v. FDA. In Coyne Beahm, the District Court held that the Federal Food, Drug, and Cosmetic Act authorized the FDA to regulate tobacco products, but not tobacco advertising. The Fourth Circuit rejected the District Court's jurisdictional ruling and invalidated the FDA's regulations in their entirety. The Clinton Administration has since requested an en banc rehearing before the Fourth Circuit. PMID:10557544

Drug shortages are threatening care quality and cost-containment efforts. I describe the pharmaceutical marketplace changes that have caused the problem, and propose new policies to solve it, through changing incentives for producers and purchasers. I propose a grading scheme for the Food and DrugAdministration when it inspects manufacturing facilities in the United States and abroad. The inspections’ focus would change from closing unsafe plants to improving production process quality, reducing the likelihood that plants will be closed—the most frequent cause of drug shortages. PMID:23488502

The discovery, development, and marketing of drugs for clinical use is a process that is complex, arduous, expensive, highly regulated, often criticized, and sometimes controversial. In the United States, the Food and DrugAdministration (FDA) is the governmental agency responsible for regulating the development and marketing of drugs, medical devices, biologics, foods, cosmetics, radiation-emitting electronic devices, and veterinary products, with the objective of ensuring their safety and efficacy. As part of a broad overview of the drug development process, this article will describe the historical evolution of the FDA. This will provide background for two subsequent articles in this series, which will describe the ethical foundations of clinical research and hethe stages of drug development. PMID:18251347

Intrathecal drugadministration system (ITDAS) can reduce the side effects while increasing the effectiveness of opioids compared to systemic opioid administration. Therefore, the use of ITDAS has increased in the management of cancer pain and chronic intractable pain. Catheter obstruction is a serious complication of ITDAS. Here, we present a case of catheter obstruction by a mass formed at the side hole and in the lumen. A 37-year-old man suffering from failed back surgery syndrome received an ITDAS implantation, and the ITDAS was refilled with morphine every 3 months. When the patient visited the hospital 18 months after ITDAS implantation for a refill, the amount of delivered morphine sulfate was much less than expected. Movement of the pump rotor was examined with fluoroscopy; however, it was normal. CSF aspiration through the catheter access port was impossible. When the intrathecal catheter was removed, we observed that the side hole and lumen of the catheter was plugged. PMID:22259717

The vaccine-approval process in the United States is regulated by the Center for Biologics Evaluation and Research of the US Food and DrugAdministration. Throughout the life cycle of development, from preclinical studies to after licensure, vaccines are subject to rigorous testing and oversight. Manufacturers must adhere to good manufacturing practices and control procedures to ensure the quality of vaccines. As mandated by Title 21 of the Code of Regulations, licensed vaccines must meet stringent criteria for safety, efficacy, and potency. PMID:21502242

... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and DrugAdministration Science Board to the Food and DrugAdministration; Notice of Meeting AGENCY: Food and DrugAdministration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public advisory committee of...

... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and DrugAdministration Science Board to the Food and DrugAdministration; Notice of Meeting AGENCY: Food and DrugAdministration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public advisory committee of...

... HUMAN SERVICES Food and DrugAdministration Science Board to the Food and DrugAdministration; Notice of... to the public. Name of Committee: Science Board to the Food and DrugAdministration (Science Board). General Function of the Committee: The Science Board provides advice primarily to the Commissioner of...

... HUMAN SERVICES Food and DrugAdministration Science Board to the Food and DrugAdministration; Notice of... to the public. Name of Committee: Science Board to the Food and DrugAdministration (Science Board). General Function of the Committee: The Science Board provides advice primarily to the Commissioner of...

... HUMAN SERVICES Food and DrugAdministration Science Board to the Food and DrugAdministration; Notice of... to the public. Name of Committee: Science Board to the Food and DrugAdministration (Science Board). General Function of the Committee: The Science Board provides advice primarily to the Commissioner of...

... reportable food that is the subject of a summary posting and that are part of a chain of establishments with... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration Food Safety Modernization Act: Focus on Inspections and Compliance AGENCY: Food and DrugAdministration, HHS. ACTION: Notice of...

Expanded Programme on Immunisation (EPI) vaccination rates remain well below herd immunity in regions of many countries despite huge international resources devoted to both financing and access. We draw upon service marketing theory, organisational sociology, development anthropology and cultural consumer research to conduct an ethnographic study of vaccination delivery in Jimma Zone, Ethiopia - one such region. We find that Western public health sector policies are dominated by an administrative logic. Critical failures in delivery are produced by a system that obfuscates the on-the-ground problems that mothers face in trying to vaccinate their children, while instead prioritising administrative processes. Our ethnographic analysis of 83 mothers who had not vaccinated their children reveals key barriers to vaccination from a 'customer' perspective. While mothers value vaccination, it is a 'low involvement' good compared to the acute daily needs of a subsistence life. The costs imposed by poor service - such as uncaring staff with class hostilities, unpredictable and missed schedules and long waits - are too much and so they forego the service. Our service design framework illuminates specific service problems from the mother's perspective and points towards simple service innovations that could improve vaccination rates in regions that have poor uptake. PMID:25363481

.99) with the observed values in the SD rat corneas. Similar pharmacokinetics models explain drug delivery to the cornea in rat and rabbit animal models. Retinal pharmacokinetics after periocular drugadministration can be explained with a four-compartment (periocular space, choroid-containing transfer compartment, retina, and distribution compartment) model with elimination from the periocular space, retina, and choroid compartment. Inclusion of a dissolution–release step before the drug is available for absorption or elimination better explains retinal tmax. Good fits were obtained in both the BN (r = 0.99) and SD (r = 0.99) rats for retinal celecoxib using the same model; however, the parameter estimates differed. Conclusions Corneal and retinal pharmacokinetics of small lipophilic molecules after periocular administration can be described by compartment models. The modeling analysis shows that (1) leak-back from the site of administration most likely contributes to the apparent lack of an increase phase in corneal concentrations; (2) elimination via the conjunctival or periocular blood and lymphatic systems contributes significantly to drug clearance after periocular injection; (3) corneal pharmacokinetics of small lipophilic molecules can be explained by using similar models in rats and rabbits; and (4) although there are differences in some retinal pharmacokinetics parameters between the pigmented and nonpigmented rats, the physiological basis of these differences has yet to be ascertained. PMID:18172109

7 of 8 dogs receiving combination drug therapy consisting of flucytosine together with amphotericin B and/or a triazole for cryptococcosis or aspergillosis developed cutaneous or mucocutaneous eruptions during the course of treatment. Lesions resolved in all cases following discontinuation of flucytosine despite continued administration of other antifungals, suggesting the eruption was referable primarily to the flucytosine component of therapy. Lesions developed 13 to 41 days (median 20 days) after commencing flucytosine (105 to 188 mg/kg/day divided and given every 8 h; median dose rate 150 mg/kg/day). The cumulative dose of flucytosine given prior to the first signs of the drug eruption ranged from 1.7 to 6.8 g/kg (median 2.3 g/kg). The eruptions consisted of depigmentation, followed by ulceration, exudation and crust formation. The scrotum was affected in all 4 male dogs, the nasal plane in 6 of 7 cases, while the lips, vulva, external ear canal and integument were involved in a smaller number of cases. There was considerable variation in the severity of lesions, with changes being most marked when flucytosine was continued for several days after lesions first appeared. Some dogs experienced malaise and inappetence in association with the suspected drug eruption. Healing took a variable period, typically in excess of 2 weeks after discontinuing flucytosine, with up to 2 months being required for total resolution of the lesions. All lesions resolved eventually without scarring or permanent loss of pigment. PMID:8937669

In times of financial and economic crises, public organizations seem to cut their budgets for training and education, especially when the impact of a programme is questioned. Therefore, PA programmes need to clarify what impact can be expected and what individual and organizational processes are influencing the impact of a PA programme on the…

Drugadministration is one of the main sources of errors in pediatric intensive care units (PICUs). An available guide for intravenous drugadministration might be useful. The aim of this article is to present the methodology and results for the development of a guide for intravenous drugadministration in a PICU. A total of 116 drugs were included. Standard concentrations, diluents, technique for reconstitution and dilution, stability, rate of administration, and relevant observations were defined for each drug according to a review of the most commonly used literature resources. The main unique feature of this article is that it includes standard concentrations for each drug. PMID:24384883

The current strategy for the interruption of transmission of lymphatic filariasis in areas where the disease is co-endemic with onchocerciasis is repeated annual mass treatment of endemic communities with ivermectin and albendazole. These drugs are not recommended for use in pregnancy. Pregnant women are excluded on the basis of their last menses. This exclusion criterion based on recall carries some inherent errors, leading sometimes to inadvertent exposure of foetuses to these drugs. This study set out to document the extent of inadvertent exposure of pregnant women to albendazole and ivermectin and assess the relative risk of congenital malformations because of inadvertent treatment with these drugs in early pregnancy. The study was conducted in the Ahanta West District of Ghana. Local pregnancy revelation norms were studied, followed by a household survey of women aged 15-45 years to assess drugadministration coverage. All infants born within 42 weeks of the mass drug treatment were examined to document any congenital malformations. Mothers who had lost any such infants responded to a verbal autopsy to ascertain the probable cause of death. Health facilities and local Traditional Birth Attendants were also visited to review maternity records. Of 2985 women of childbearing age (15-49 years) who were interviewed, 343 were pregnant during the mass drugadministration. The sensitivity of the last menstrual period in detecting pregnancy and thus being excluded from treatment was 0.854 (293 of 343). Some pregnant women 50 of 343 (14.6%) had thus been inadvertently treated. This represents 1.7% of women in fertile age group (15-49 years). Of the six children found with some congenital malformations in these communities, one had been exposed to the drugs in-utero. The relative risk for congenital malformation after exposure was 1.05 (P=1.0). Two of nine reported spontaneous abortions had been exposed to the drugs (P=0.62). We conclude that the local mode of excluding

Factors which influence students' selection of a Master of Business Administrationprogramme are identified and the variation in their relative importance across the student population investigated. This research also identifies the features of a university which attracts students, as well as examining the students' perceptions of the management…

Objectives: Timely and accurate health data are important for objective decision making and policy formulation. However, little evidence exists to explain why poor quality routine health data persist. This study examined the constraints to data reporting for the lymphatic filariasis mass drugadministrationprogramme in two districts in Ghana. This qualitative study focused on timeliness and accuracy of mass drugadministration reports submitted by community health volunteers. Methods: The study is nested within a larger study focusing on the feasibility of mobile phone technology for the lymphatic filariasis programme. Using an exploratory study design, data were obtained through in-depth interviews (n = 7) with programme supervisors and focus group discussions (n = 4) with community health volunteers. Results were analysed using thematic content analysis. Results: Reasons for delays in reporting were attributed to poor numeracy skills among community health volunteers, difficult physical access to communities, high supervisor workload, poor adherence reporting deadlines, difficulty in reaching communities within allocated time and untimely release of programme funds. Poor accuracy of data was mainly attributed to inadequate motivation for community health volunteers and difficulty calculating summaries. Conclusion: This study has shown that there are relevant issues that need to be addressed in order to improve the quality of lymphatic filariasis treatment coverage reports. Some of the factors identified are problems within the health system; others are specific to the community health volunteers and the lymphatic filariasis programme. Steps such as training on data reporting should be intensified for community health volunteers, allowances for community health volunteers should be re-evaluated and other non-monetary incentives should be provided for community health volunteers. PMID:26770791

Mass spectrometry-based in vitro diagnostic devices that measure proteins and peptides are underutilized in clinical practice, and none has been cleared or approved by the Food and DrugAdministration (FDA) for marketing or for use in clinical trials. One way to increase their utilization is through enhanced interactions between the FDA and the clinical mass spectrometry community to improve the validation and regulatory review of these devices. As a reference point from which to develop these interactions, this article surveys the FDA's regulation of mass spectrometry-based devices, explains how the FDA uses guidance documents and standards in the review process, and describes the FDA's previous outreach to stakeholders. Here we also discuss how further communication and collaboration with the clinical mass spectrometry communities can identify opportunities for the FDA to provide help in the development of mass spectrometry-based devices and enhance their entry into the clinic. PMID:26553791

Objectives To examine the relationship between a belief about Food and DrugAdministration (FDA) safety evaluation of cigarettes and smoking risk perceptions. Methods A nationally representative, random-digit-dialed telephone survey of 1046 adult current cigarette smokers. Results Smokers reporting that the FDA does not evaluate cigarettes for safety (46.1%), exhibited greater comprehension of the health risks of smoking and were more likely (48.5%) than other participants (33.6%) to report quit intentions. Risk perceptions partially mediated the relationship between FDA evaluation belief and quit intentions. Conclusions These findings highlight the need for proactive, effective communication to the public about the aims of new tobacco product regulations. PMID:22251767

A workshop sponsored by the Food and DrugAdministration (FDA) was held on March 4-5, 1996, at the Lister Hill Auditorium of the National Institutes of Health (NIH) Campus in Bethesda, Maryland. The workshop considered both the scientific aspects and the regulatory implications of indirect-acting carcinogens. A wide variety of agents and of prospective mechanisms was discussed. The organizing committee for the workshop consisted of Drs. James Farrelly and Joseph DeGeorge of the Center for Drug Evaluation and Research (CDER), Ronald J. Lorentzen and Sidney Green of the Center for Food Safety and Applied Nutrition (CFSAN), Martin D. Green of the Center for Biologics, Evaluation and Research (CBER), C. Darnell Jackson and Lionel A. Poirier of the National Center for Toxicological Research (NCTR). Rosalie K. Elespuru of the Center for Devices and Radiological Health (CDRH), and David G. Longfellow of the National Cancer Institute (NCI). Following an introduction by Dr. Poirier, who provided a description of indirect carcinogens, the major talks were grouped into three formal sessions: indirect-acting compounds and agents of FDA interest, biological and biochemical endpoints commonly seen with indirect agents, and specific problems associated with the indirect-acting compounds. A panel discussion followed and the concluding remarks were made by Dr. Bernard A. Schwetz, Associate Commissioner for Science, FDA. PMID:8923694

The problems associated with neglected diseases are often compounded by increasing incidence of antibiotic resistance. Patient negligence and abuse of antibiotics has lead to explosive growth in cases of tuberculosis, with some M. tuberculosis strains becoming virtually untreatable. Structure-based drug development is viewed as cost-effective and time-consuming method for discovery and development of hits to lead compounds. In this review we will discuss the suitability of fragment-based methods for developing new chemotherapeutics against neglected diseases, providing examples from our tuberculosis programme.

.... ACTION: Final rule. SUMMARY: Under delegated authority, the Administrator of the Drug Enforcement... Substances Act and subsequently delegated to the Administrator of DEA. DATES: Effective Dates: This Final... Attorney General has delegated his functions under the CSA to the Administrator of the Drug...

... HUMAN SERVICES Food and DrugAdministration Science Board to the Food and DrugAdministration: Request... Administration (FDA) is requesting nominations to serve on the Science Board to FDA (Science Board). FDA seeks to... given first consideration for membership on the Science Board. Nominations received after October...

Mass drugadministration (MDA) is a means of delivering safe and inexpensive essential medicines based on the principles of preventive chemotherapy, where populations or sub-populations are offered treatment without individual diagnosis. High-coverage MDA in endemic areas aims to prevent and alleviate symptoms and morbidity on the one hand and can reduce transmission on the other, together improving global health. MDA is the recommended strategy of the World Health Organisation to control or eliminate several neglected tropical diseases (NTDs). More than 700 million people now receive these essential NTD medicines annually. The combined cost of integrated NTD MDA has been calculated to be in the order of $0.50 per person per year. Activities have recently been expanded due, in part, to the proposed attempt to eliminate certain NTDs in the coming two decades. More than 1.9 billion people need to receive MDA annually across several years if these targets are to be met. Such extensive coverage will require additional avenues of financial support, expanded monitoring and evaluation focusing on impact and drug efficacy, as well as new diagnostic tools and social science strategies to encourage adherence. MDA is a means to help reduce the burden of disease, and hence poverty, among the poorest sector of populations. It has already made significant improvements to global health and productivity and has the potential for further successes, particularly where incorporated into sanitation and education programmes. However logistical, financial and biological challenges remain. PMID:24821920

Lymphatic filariasis has been targeted for elimination by 2020, and a threshold of 65% coverage of mass drugadministration (MDA) has been adopted by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A recent review by Babu and Babu of 36 studies of MDA for lymphatic filariasis in India found that coverage, defined as receipt of tablets, ranged from 48.8 to 98.8%, while compliance, defined as actual ingestion of tablets, was 22% lower on average. Moreover, the denominator for these coverage figures is the eligible, rather than total, population. By contrast, the 65% threshold, in the original modelling study, refers to ingestion of tablets in the total population. This corresponds to GPELF's use of ‘epidemiological drug coverage’ as a trigger for the Transmission Assessment Surveys (TAS), which indicate whether to proceed to post-MDA surveillance. The existence of less strict definitions of ‘coverage’ should not lead to premature TAS that could impair MDA's sustainability. PMID:25575555

The actions and regulations of the Food and DrugAdministration (FDA) are crucial to the entire population of the U.S., specifically the public who take a multitude of drugs and providers who prescribe drugs and devices. Further, the FDA is relevant to investors, specifically in regards to biotech and pharmaceutical companies involved in developing new drugs. The FDA has been criticized for a lack of independence on the one hand and excessive regulatory and expanding authority without evidence and consistency of the actions on the other hand. The FDA approved a single-entity, long-acting, hydrocodone product (Zohydro, Zogenix, San Diego, CA) on October 25, 2013, against the recommendation of the FDA's own appointed scientific advisory panel, which voted 11 to 2 against the approval of Zohydro. Subsequent to the approval, multiple consumer safety organizations, health care agencies, addiction treatment providers, professional organizations, and other groups on the frontline of the opioid addiction epidemic have expressed concern. In addition, the US Congress and various state attorneys general raised serious concerns about the approval of Zohydro, which is highly addictive and may enhance the opioid addiction epidemic. Supporters of Zohydro contend that it is necessary and essential to manage chronic pain and improve functional status with no additional risk. Over the past 15 years, prescriptions for opioids have skyrocketed with the United States consuming more than 84% of the global oxycodone and more than 99% of the hydrocodone supply. The sharp increase in opioid prescribing has led to parallel increases in opioid addiction and overdose deaths, surpassing motor vehicle injuries in the U.S. Recent studies assessing the trends of medical use and misuse of opioid analgesics from 2000 to 2011 have concluded that the present trend of the continued increase in the medical use of opioid analgesics appears to contribute to increasing misuse, resulting in multiple health

In the United States Court of Appeals of the District of Columbia Circuit, the Appellants Mom's Against Mercury, Connecticut Coalition for Environmental Justice, Oregonians for Life, California Citizens for Health Freedom, Kevin J. Biggers, Karen Johnson, Linda Brocato, R. Andrew Landerman, and Antia Vazquez Tibaul filed a petition for review of Regulatory Inaction by the Food and DrugAdministration (FDA). On Monday June 2, 2008, the lawsuit was settled with the FDA after it agreed to classify mercury fillings. During its negotiation session with the Appellants, the FDA indicated that it would change its website on mercury fillings. The FDA no longer claims that no science exists about the safety of mercury amalgam or that other countries have acted for environmental reasons only. On its website, the FDA now states the following: "Dental amalgams contain mercury, which may have neurotoxic effects on the nervous systems of developing children and fetus." The FDA also states that "Pregnant women and persons who may have a health condition that makes them more sensitive to mercury exposure, including individuals with existing high levels of mercury bioburden, should not avoid seeking dental care, but should discuss options with their health practitioner." The FDA decision to classify mercury fillings is a reflection of the legislations enacted in Europe and Canada that highlight the neurotoxic effects of mercury fillings. PMID:19105536

In 2008 in Morogoro region, Tanzania, mass drugadministration (MDA) to school-aged children to treat two neglected tropical diseases (NTDs) - urinary schistosomiasis and soil-transmitted helminths - was suspended by the Ministry of Health and Social Welfare after riots broke out in schools where drugs were being administered. This article discusses why this biomedical intervention was so vehemently rejected, including an eyewitness account. As the protest spread to the village where I was conducting fieldwork, villagers accused me of bringing medicine into the village with which to 'poison' the children and it was necessary for me to leave immediately under the protection of the Tanzanian police. The article examines the considerable differences between biomedical and local understandings of one of these diseases, urinary schistosomiasis. Such a disjuncture was fuelled further by the apparent rapidity of rolling out MDA and subsequent failures in communication between programme staff and local people. Rumours of child fatalities as well as children's fainting episodes and illnesses following treatment brought about considerable conjecture both locally and nationally that the drugs had been either faulty, counterfeit, hitherto untested on humans or part of a covert sterilization campaign. The compelling arguments by advocates of MDA for the treatment of NTDs rest on the assumption that people suffering from these diseases will be willing to swallow the medicine. However, as this article documents, this is not always the case. For treatment of NTDs to be successful it is not enough for programmes to focus on economic and biomedical aspects of treatment, rolling out 'one size fits all' programmes in resource-poor settings. It is imperative to develop a biosocial approach: to consider the local social, biological, historical, economic and political contexts in which these programmes are taking place and in which the intended recipients of treatment live their lives

Although the number of new drug shortages has been lower in recent years than in the past, severe shortages have occurred that have affected large numbers of patients. A new law entitled the Food and DrugAdministration Safety and Innovation Act was enacted in July of 2012, which requires companies to notify the Food and DrugAdministration of anticipated shortages. This notification requirement has allowed the Food and DrugAdministration to work closely with manufacturers earlier to mitigate and, often, prevent shortages. However, not all shortages are able to be prevented, and the shortage of peritoneal dialysis solution is one that has had a significant effect on patients. The Food and DrugAdministration continues to use all available tools to address this shortage with manufacturers, including temporary availability of imported peritoneal dialysis solution from Ireland. Mitigating shortages is a top priority for the Food and DrugAdministration, and communication with all stakeholders is essential. PMID:25896999

...: The public conference will be held on the campus of Xavier University, 3800 Victory Pkwy., Cincinnati... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration/Xavier University Global... University, is announcing a public conference entitled ``FDA/Xavier University Global Medical...

... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration/Xavier University Global... University, is announcing a public conference entitled ``FDA/Xavier University Global Medical Device... public conference will be held on the campus of Xavier University, 3800 Victory Pkwy., Cincinnati,...

... conference will be held on the campus of Xavier University, 3800 Victory Pkwy., ] Cincinnati, OH 45207, 513... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration/Xavier University Global... University, is announcing a public conference entitled ``FDA/Xavier University Global Medical...

... public conference will be held on the campus of Xavier University, 3800 Victory Pkwy., Cincinnati, OH... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration/Xavier University Global... University, is announcing a public conference entitled ``FDA/Xavier University Global Medical...

... Food and DrugAdministration Staff; Design Considerations for Pivotal Clinical Investigations for... and DrugAdministration (FDA) is announcing the availability of the draft guidance entitled ``Design... study design principles relevant to the development of medical device clinical studies that can be...

... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration Clinical Trial Requirements... public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration Clinical Trial Requirements... workshop. The public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration Clinical Trial Requirements... announcing a public workshop entitled ``FDA Clinical Trial Requirements, Regulations, Compliance, and Good... representatives. The program will focus on the relationships among the FDA and clinical trial staff,...

... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration Clinical Trial Requirements... workshop. The public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration Clinical Trial Requirements... public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration Clinical Trial Requirements... workshop. The public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration Clinical Trial Requirements... public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration Transparency Task Force... transparent, collaborative, and participatory government. FDA has formed an internal Transparency Task Force..., the Task Force has held two public meetings, on June 24, 2009, and November 3, 2009, and established...

..., (76 FR 3825, January 21, 2011), FDA recounted the actions it had already implemented, as well as those... of availability of this report on October 4, 2011 (76 FR 61366), FDA sought public comment on these... HUMAN SERVICES Food and DrugAdministration Food and DrugAdministration Transparency...

Anesthetics and psychoactive drugs could relieve diseases, if used properly. However, they can cause dependency, and their misuse or abuse could adversely affect people's health and social stability. For a long time, the Chinese government has been reinforcing the regulation on anesthetics and psychoactive drugs to ensure their legal and proper usage, and to prevent abuse. The state council issued 'the regulations on the administration of anesthetic drugs and psychotropic drugs' in 2005, based on which a legal system was established for administration of anesthetics and psychoactive drugs with the objectives of ensuring their legitimate medical utilization, and preventing illegal abuse. PMID:26068438

Acts of three Texas Legislatures have mandated that the schools of Texas provide a program for all public school students, grades K-12, in crime prevention and drug education. To assist schools in formulating a philosophy about and in developing appropriate programs and techniques for drug education and crime prevention programs, the Texas…

Background: There has been a significant increase in the prevalence of autism in the USA in the past few decades. The purpose of this study was to provide recent estimates of psychotropic drug use and costs among individuals with autism enrolled in the Medicaid programme. Method: A cross-sectional analysis of 2007 Mississippi (MS) Medicaid…

Drugs delivery by subcutaneous injection is often the last resort/appeal for a doctor anxious to limit the aggressive and invasive treatments, particularly within palliative care. A review was made to list the drugs which can be administered by this route. Concerned antibiotics are teicoplanin, netilmicin and gentamicin with a risk of skin necrosis for aminoglycosids. Midazolam is useful in various indications and can be associated with morphine in case of dyspnoea. Data about subcutaneous injection of dexamethasone, clonazepam, haloperidol and levomepromazine are published; it is the same for fentanyl, nefopam, ondansetron and metoclopramide. The subcutaneous injection of these quoted drugs is possible, but requires further studies. PMID:21176759

Mass treatment is the most convenient way to combat fish diseases. For example, drugs can be administered per os in diets, or chemicals can be added to the water. These methods are mostly ineffective in treating systemic infections of adult salmon because mature salmon do not feed, and many fish diseases cannot be controlled by chemical baths. Thus, effective treatment would require administering drugs to each individual.

The Food and DrugAdministration (FDA or Agency) is implementing its authority to destroy a drug valued at $2,500 or less (or such higher amount as the Secretary of the Treasury may set by regulation) that has been refused admission into the United States under the Federal Food, Drug, and Cosmetic Act (the FD&C Act), by issuing a rule that provides to the owner or consignee notice and an opportunity to appear and introduce testimony to the Agency prior to destruction. This regulation is authorized by amendments made to the FD&C Act by the Food and DrugAdministration Safety and Innovation Act (FDASIA). Implementation of this authority will allow FDA to better protect the public health by providing an administrative process for the destruction of certain refused drugs, thus increasing the integrity of the drug supply chain. PMID:26387150

Administration of drugs directly into the respiratory tree first was proposed a long time ago. Surfactant is the paradigmatic example of such therapies. Many other drugs have been used in the same way and further compounds are under investigation for this aim. In the last two decades, despite the wide number of drugs available for direct lung administration in critical care patients, few controlled data exist regarding their use in neonates and infants. This review will focus on drugs clinically available in a critical care setting for neonates and infants, including bronchodilators, pulmonary vasodilators, anti-inflammatory agents, mucolytics, resuscitative anti-infective agents, surfactants and other drugs. We provide an evidence-based comprehensive review of drugs available for intratracheal administration in paediatric and neonatal critical care and we examine possible advantages and risks for each proposed indication. PMID:21357925

Land management and land administration are defined as a system of planning, management and administration methods and techniques that aims to integrate ecological with social, economic and legal principles in the management of land for urban and rural development purposes. The main objective is to meet changing and developing human needs, while…

In 1992, New York State Department of Health regulations provided for fully legal syringe exchange programmes in the state. The policies and procedures mandated that: 'Each program must seek to recruit ... for inclusion on its advisory board ... program participants ... Programs are also urged to establish other advisory bodies, such as Users' Advisory Boards made up of program participants, to provide input and guidance on program policies and operations.' The inclusion of drug users as official advisors to the legal programmes was seen as a method for incorporating the views of the consumers of the service in operational decisions. The 1992 regulations implied a new public image for users of illicit psychoactive drugs: active drug users were seen to be capable not only of self-protective actions (such as avoiding HIV infection), but also of serving as competent collaborators in programmes to preserve the public health. This development has important implications with regard to the evolution of official drug policy, since it will be difficult in future to treat IDUs simply as the passive objects of state intervention. Whether as individuals or representatives of a wider population of illicit drug users, they have acquired a legitimacy and sense of personal worth which would have been unthinkable in previous periods. PMID:9828960

Multiple drugadministration is an important aspect of clinical practice particularly in specific physiological situation such as in neonates, elderly or pregnancy, since in all such situations, possibility of unwanted effects increases due to altered body physiology. In present study, the teratogenic effects of multiple drugadministration risperidone, meclizine/pyridoxine and hydralazine have been compared with the teratogenic effects of individual drugs in pregnant mice. Moreover the role of folic acid and α-tocopherol if any had also been investigated in reducing the teratogenic effects of these drugs in combinations. PMID:22186339

The statutory standards underlying the activities of the FDA, and the problems the Agency faces in decision making are discussed from a legal point of view. The premarketing clearance of new drugs and of food additives, the two most publicized and criticized areas of FDA activity, are used as illustrations. The importance of statutory standards in technology assessment in a regulatory setting is developed. The difficulties inherent in the formulation of meaningful standards are recognized. For foods, the words of the statute are inadequate, and for drugs, a statutory recognition of the various other objectives would be useful to the regulator and the regulated.

Context: Drug-induced pancreatitis (DIP) is rare, but as there are no systematic data on it, the true incidence is not known. Although numerous and varied drugs have been associated with DIP, the clinical evidence on doxycycline-induced pancreatitis is sparse. Case Report: We present the case of a 58-year-old female who presented with complaints of nausea and severe epigastric pain. Her medications included doxycycline which she had been on for only 2 days. Computed tomography of her abdomen showed mild enlargement of body of the pancreas with peripancreatic fatty infiltration, along with lipase level suggestive of acute pancreatitis. In the absence of classical risk factors for acute pancreatitis, a diagnosis of DIP secondary to doxycycline therapy was made. Immediate withdrawal of the drug was accompanied by relief of symptoms and resolution of pancreatitis. Conclusion: This report implicates doxycycline as an etiological factor for acute pancreatitis. Knowledge regarding doxycycline related pancreatitis is of paramount importance in order to diagnose cases early and institute effective treatment in patients who are undergoing therapy with this drug. PMID:27042611

... and DrugAdministration and Servicio Nacional de Sanidad, Inocuidad y Calidad Agroalimentaria of the... Sanidad, Inocuidad y Calidad Agroalimentaria of the United Mexican States. The purpose of the MOU is...

... DrugAdministration and the Inter-American Institute for Cooperation in Agriculture AGENCY: Food and... Agriculture. The purpose of the arrangement is to provide a framework between the two Agencies to...

Administering medication per rectum can be the most appropriate route for some patients may not always be considered by health professionals. Cultural sensitivities, as well as misinformation regarding insertion methods, may be barriers to the practice. This article explains how the rectal route functions in drug absorption, clarifies when this route is appropriate to use and outlines the steps nurses should follow to prepare patients adequately and safely to carry out the procedure. PMID:27071237

Background As part of the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drugadministration (MDA) from 2000–2006, and passed transmission assessment surveys in 2011–2012. We examined the seroprevalence and spatial epidemiology of LF post-MDA to inform strategies for ongoing surveillance and to reduce resurgence risk. Methods ELISA for LF antigen (Og4C3) and antibodies (Wb123, Bm14) were performed on a geo-referenced serum bank of 807 adults collected in 2010. Risk factors assessed for association with sero-positivity included age, sex, years lived in American Samoa, and occupation. Geographic clustering of serological indicators was investigated to identify spatial dependence and household-level clustering. Results Og4C3 antigen of >128 units (positive) were found in 0.75% (95% CI 0.3–1.6%) of participants, and >32 units (equivocal plus positive) in 3.2% (95% CI 0.6–4.7%). Seroprevalence of Wb123 and Bm14 antibodies were 8.1% (95% CI 6.3–10.2%) and 17.9% (95% CI 15.3–20.7%) respectively. Antigen-positive individuals were identified in all ages, and antibody prevalence higher in older ages. Prevalence was higher in males, and inversely associated with years lived in American Samoa. Spatial distribution of individuals varied significantly with positive and equivocal levels of Og4C3 antigen, but not with antibodies. Using Og4C3 cutoff points of >128 units and >32 units, average cluster sizes were 1,242 m and 1,498 m, and geographical proximity of households explained 85% and 62% of the spatial variation respectively. Conclusions High-risk populations for LF in American Samoa include adult males and recent migrants. We identified locations and estimated the size of possible residual foci of antigen-positive adults, demonstrating the value of spatial analysis in post-MDA surveillance. Strategies to monitor cluster residents and high-risk groups are needed to reduce resurgence risk. Further research is required to

Background: Medication errors can result in harm, unless barriers to prevent them are present. Drugadministration errors are less likely to be prevented, because they occur in the last stage of the drug distribution process. This is especially the case in non-alert patients, as patients often form the final barrier to prevention of errors.…

... DrugAdministration (FDA) published in the Federal Register of March 23, 2012 (77 FR 16923), a direct... Agency received significant adverse comment. DATES: The direct final rule published at 77 FR 16923, March... and Drugs, the direct final rule published in the Federal Register on March 23, 2012 (77 FR 16923)...

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Food and DrugAdministration Division of Freedom... Division of Freedom of Information. (a) The office responsible for Agency compliance with the Freedom of Information Act and this part is the Division of Freedom of Information (ELEM-1029), Food and...

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Food and DrugAdministration Division of Freedom... Division of Freedom of Information. (a) The office responsible for Agency compliance with the Freedom of Information Act and this part is the Division of Freedom of Information (ELEM-1029), Food and...

... Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUGADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20... opinions, as well as orders, made in the adjudication of cases; (2) Statements of policy and...

... Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUGADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20... opinions, as well as orders, made in the adjudication of cases; (2) Statements of policy and...

... Public Reading Rooms. 20.120 Section 20.120 Food and Drugs FOOD AND DRUGADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20... opinions, as well as orders, made in the adjudication of cases; (2) Statements of policy and...

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Agreements between the Food and DrugAdministration and other departments, agencies, and organizations. 20.108 Section 20.108 Food and Drugs FOOD AND DRUGADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records §...

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Testing and research conducted by or with funds provided by the Food and DrugAdministration. 20.105 Section 20.105 Food and Drugs FOOD AND DRUGADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.105 Testing...

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Testing and research conducted by or with funds provided by the Food and DrugAdministration. 20.105 Section 20.105 Food and Drugs FOOD AND DRUGADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.105 Testing...

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Testing and research conducted by or with funds provided by the Food and DrugAdministration. 20.105 Section 20.105 Food and Drugs FOOD AND DRUGADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PUBLIC INFORMATION Availability of Specific Categories of Records § 20.105 Testing...

... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND... Administration, United States Department of Health and Human Services and the National Alliance for Hispanic Health AGENCY: Food and DrugAdministration, HHS. ACTION: Notice. SUMMARY: The Food and...

... surveillance processes, including application submission, review, compliance with good manufacturing practices... good manufacturing practices (CGMP) for PET drugs. The procedures were finalized and an implementation...://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm085783.htm . Recognizing that many...

Introduction To date, there is no evidence showing a benefit from any advanced cardiac life support (ACLS) medication in out-of-hospital cardiac arrest (OOHCA), despite animal data to the contrary. One explanation may be a difference in the time to first drugadministration. Our previous work has shown the mean time to first drugadministration in clinical trials is 19.4 minutes. We hypothesized that the average time to drugadministration in large animal experiments occurs earlier than in OOHCA clinical trials. Methods We conducted a literature review between 1990 and 2006 in MEDLINE using the following MeSH headings: swine, dogs, resuscitation, heart arrest, EMS, EMT, ambulance, ventricular fibrillation, drug therapy, epinephrine, vasopressin, amiodarone, lidocaine, magnesium, and sodium bicarbonate. We reviewed the abstracts of 331 studies and 197 full manuscripts. Exclusion criteria included: non-peer reviewed, all without primary animal data, and traumatic models. From these, we identified 119 papers that contained unique information on time to medication administration. The data are reported as mean, ranges, and 95% confidence intervals. Mean time to first drugadministration in animal laboratory studies and clinical trials was compared with a t-test. Regression analysis was performed to determine if time to drug predicted ROSC. Results Mean time to first drugadministration in 2378 animals was 9.5 minutes (range 3.0–28.0; 95% CI around mean 2.78, 16.22). This is less than the time reported in clinical trials (19.4 min, p<0.001). Time to drug predicted ROSC (Odds Ratio 0.844; 95% CI 0.738, 0.966). Conclusion Shorter drug delivery time in animal models of cardiac arrest may be one reason for the failure of animal studies to translate successfully into the clinical arena. PMID:17360097

This is part 2 of a 2-part article on the topic of Nominations of Difficult to Compound Drugs to the FDA-PCAC. Part 1 provided a current list of Nominations of Difficult to Compound Drugs to the FDA-PCAC. This article discusses the evaluation procedure for determining which drugs are demonstrably difficult to compound. PMID:26891563

The Food and DrugAdministration (FDA) is classifying the laser fluorescence caries detection device into class II (special controls). The special controls that will apply to this device are set forth below. The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the amendments), the Safe Medical Devices Act of 1990, and the Food and DrugAdministration Modernization Act of 1997. The agency is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. PMID:11010622

Lymphatic filariasis is one of several neglected tropical diseases with severely disabling and stigmatizing manifestations that are referred to as 'neglected diseases of poverty'. It is a mosquito-borne disease found endemically and exclusively in low-income contexts where, concomitantly, general public health care is often deeply troubled and fails to meet the basic health needs of impoverished populations. This presents particular challenges for the implementation of mass drugadministration (MDA), which currently is the principal means of control and eventual elimination. Several MDA programmes face the dilemma that they are unable to attain and maintain the required drug coverage across target groups. In recognition of this, a qualitative study was conducted in the Morogoro and Lindi regions of Tanzania to gain an understanding of community experiences with, and perceptions of, the MDA campaign implemented in 2011 by the National Lymphatic Filariasis Elimination Programme. The study revealed a wide variation of perceptions and experiences regarding the aim, rationale and justification of MDA. There were positive sentiments about the usefulness of the drugs, but many study participants were sceptical about the manner in which MDA is implemented. People were particularly disappointed with the limited attempts by implementers to share information and mobilize residents. In addition, negative sentiments towards MDA for lymphatic filariasis reflected a general feeling of desertion and marginalization by the health care system and political authorities. However, the results suggest that if the communities are brought on board with genuine respect for their integrity and informed self-determination, there is scope for major improvements in community support for MDA-based control activities. PMID:25790081

Aims The aim of this work is to understand the process of drugadministration and identify points in the workflow that resulted in interventions by clinical information systems in order to improve patient safety. Methods To identify a generic way to structure the drugadministration process we performed peer-group discussions and supplemented these discussions with a literature search for studies reporting errors in drugadministration and strategies for their prevention. Results We concluded that the drugadministration process might consist of up to 11 sub-steps, which can be grouped into the four sub-processes of preparation, personalization, application and follow-up. Errors in drug handling and administration are diverse and frequent and in many cases not caused by the patient him/herself, but by family members or nurses. Accordingly, different prevention strategies have been set in place with relatively few approaches involving e-health technology. Conclusions A generic structuring of the administration process and particular error-prone sub-steps may facilitate the allocation of prevention strategies and help to identify research gaps. PMID:24007450

A live attenuated anticoccidial vaccine (Paracox) was compared with a nicarbazin-monensin anticoccidial drug shuttle programme in three crops of Italian broilers, comprising a total of 290,405 chickens. All birds received the antibiotic growth promoter avilamycin. No coccidiosis was evident during the trials, but the occurrence of oocysts in the litter demonstrated that a natural challenge was present. Vaccinated birds consistently performed at least as well as those treated with the anticoccidial drug shuttle. The final mean weights of vaccinated birds were significantly greater (P < 0.001) than those of birds treated with anticoccidial drugs, both for females at 36/37 days and males at 56 days. Feed conversion ratios, total mortality including culls, the proportion of rejects at the processing plant, and the moisture content of the litter were not significantly different between the two control methods. Growth curves showed that there was no post-vaccinal growth check in the vaccinated birds and no intolerance of the anticoccidial drug treatment. There was no overall seasonal effect, regardless of treatment, on the performance of the three crops reared from November 1997 to July 1998. These findings suggest that the use of this vaccine is likely to enable the replacement of anticoccidial drug shuttle programmes in broilers reared under conditions similar to those used in these Italian flocks. PMID:12400552

Background Lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma are the five most prevalent neglected tropical diseases in the world, and each is frequently treated with mass drugadministrations. We performed a survey of neglected tropical diseases experts to elicit their opinions on the role of mass drugadministrations for the elimination of these infections. Methodology/Principal Findings We sent an online survey to corresponding authors who had published an article about a neglected tropical disease from 2007 to 2011. Of 825 unique authors who were invited to complete the survey, 365 (44.2%) responded, including 234 (28.4%) who answered questions regarding one of the five most prevalent neglected tropical diseases. Respondents had varying opinions about the goals of programmatic activities for their chosen neglected tropical disease, with elimination or eradication identified as the most important goal by 87% of lymphatic filariasis respondents, 66% of onchocerciasis respondents, 55% of trachoma respondents, 24% of schistosomiasis respondents, and 21% of soil-transmitted helminth respondents. Mass drugadministrations, other non-medication health measures, and education were generally thought to be more important for elimination than vector control, development of a new tool, or the presence of a secular trend. Drug resistance was thought to be a major limitation of mass drugadministrations for all five neglected tropical diseases. Over half of respondents for lymphatic filariasis and trachoma thought that repeated mass drugadministrations could eliminate infection within ten years of the initiation of mass treatments. Conclusions/Significance Respondents for lymphatic filariasis, onchocerciasis, and trachoma were more enthusiastic about the prospects of elimination and eradication than were respondents for schistosomiasis or soil-transmitted helminths. Mass drugadministrations were generally believed to be among

This double-blind, placebo-controlled study investigated effects of oral morphine (0, 45, 135 mg/70kg) and oral oxycodone (0, 15, 45 mg/70kg) in buprenorphine-maintained opioid addicts. Since a 3:1 morphine:oxycodone dose ratio had yielded equivalent subjective and physiological effects in non-dependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures, i.e. a drug vs. money and a drug vs. drug procedure, were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater compared to high-dose morphine. The study demonstrated that a 3:1 dose ratio of morphine:oxycodone was not equipotent in buprenorphine-dependent subjects. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass DrugAdministration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact. For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably. The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci. Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority. LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs.

The volume of prescription drug promotion over time is often measured by assessing changes in ad spending. However, this method obscures the fact that some types of advertising are more expensive than others. Another way to measure the changes in prescription drug promotion over time is to assess the number of promotional pieces submitted to the U.S. Food and DrugAdministration (FDA). Form FDA 2253 collects information such as the date submitted and the type of material submitted. We analyzed data from Forms FDA 2253 received from 2001–2014. We examined the frequency of submissions by audience (consumer and healthcare professional) and type of promotional material. There was a noted increase in prescription drug promotion submissions across all media in the early 2000s. Although non-Internet promotion submissions have since plateaued, Internet promotion continued to increase. These results can help public health advocates and regulators focus attention and resources. PMID:27149513

The volume of prescription drug promotion over time is often measured by assessing changes in ad spending. However, this method obscures the fact that some types of advertising are more expensive than others. Another way to measure the changes in prescription drug promotion over time is to assess the number of promotional pieces submitted to the U.S. Food and DrugAdministration (FDA). Form FDA 2253 collects information such as the date submitted and the type of material submitted. We analyzed data from Forms FDA 2253 received from 2001-2014. We examined the frequency of submissions by audience (consumer and healthcare professional) and type of promotional material. There was a noted increase in prescription drug promotion submissions across all media in the early 2000s. Although non-Internet promotion submissions have since plateaued, Internet promotion continued to increase. These results can help public health advocates and regulators focus attention and resources. PMID:27149513

Regulatory advice and assessment play an important role in the successful development of new drugs and radiopharmaceuticals for the treatment of urologic malignancies. Cooperation between the US Food and DrugAdministration (FDA) and the pharmaceutical industry has led to the approval of more than 20 new urologic oncology products in the last 2 decades. Despite these advances, more effective treatments need to be developed and approved for the treatment of urologic malignancies. This review provides general information about the FDA's role in the development of investigational new drugs, with an emphasis on the regulatory process and the requirements for marketing approval. In addition, this review summarizes the products for the treatment of urologic malignancies that were approved by the FDA in the last 30 years and the key issues concerning urologic oncology products that were discussed publicly at Oncologic Drug Advisory Committee meetings in the past 10 years. PMID:25613202

The oral administration of peptide drugs is well known to be precluded by their digestion in the stomach and small intestine. As a new approach to oral delivery, peptide drugs were coated with polymers cross-linked with azoaromatic groups to form an impervious film to protect orally administered drugs from digestion in the stomach and small intestine. When the azopolymer-coated drug reached the large intestine, the indigenous microflora reduced the azo bonds, broke the cross-links, and degraded the polymer film, thereby releasing the drug into the lumen of the colon for local action or for absorption. The ability of the azopolymer coating to protect and deliver orally administered peptide drugs was demonstrated in rats with the peptide hormones vasopressin and insulin.

SUMMARY Truncated models are indirect methods to estimate the size of a hidden population which, in contrast to the capture–recapture method, can be used on a single information source. We estimated the coverage of a tuberculosis screening programme among illicit drug users and homeless persons with a mobile digital X-ray unit between 1 January 2003 and 31 December 2005 in Rotterdam, The Netherlands, using truncated models. The screening programme reached about two-third of the estimated target population at least once annually. The intended coverage (at least two chest X-rays per person per year) was about 23%. We conclude that simple truncated models can be used relatively easily on available single-source routine data to estimate the size of a population of illicit drug users and homeless persons. We assumed that the most likely overall bias in this study would be overestimation and therefore the coverage of the targeted mobile tuberculosis screening programme would be higher. PMID:17631692

Many abused drugs can be established as orally delivered reinforcers for rhesus monkeys and other animals. Benzodiazepines, barbiturates, opioids, psychomotor stimulants, dissociative anesthetics, and ethanol can come to serve as reinforcers when taken by mouth. The principal problems in establishing drugs as reinforcers by the oral route of administration are (1) aversive taste, (2) delay in onset of central nervous system effects, and (3) consumption of low volumes of drug solution. Strategies have been devised to successfully overcome these problems, and orally delivered drugs can be established as effective reinforcers. Reinforcing actions are demonstrated by consumption of greater volumes of drug solution than volumes of the water vehicle, and supporting evidence for reinforcing effects consists of the maintenance of behavior under intermittent schedules of reinforcement and the generation of orderly dose-response functions. This article presents an overview of studies of behavior reinforced by oral drug reinforcement. Factors that control oral drug intake include dose, schedule of reinforcement, food restriction, and alternative reinforcers. Many drugs, administered by the experimenter, can alter oral drug reinforcement. Relative reinforcing effects can be assessed by choice procedures and by persistence of behavior across increases in schedule size. In general, reinforcing effects increase directly with dose. Rhesus monkeys prefer combinations of reinforcing drugs to the component drugs. The taste of drug solutions may act as a conditioned reinforcer and a discriminative stimulus. Consequences of drug intake include tolerance and physiological dependence. Findings with orally self-administered drugs are similar to many findings with other positive reinforcers, including intravenously self-administered drugs. PMID:11522433

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Testing and research conducted by or with funds... Categories of Records § 20.105 Testing and research conducted by or with funds provided by the Food and DrugAdministration. (a) Any list that may be prepared by the Food and DrugAdministration of testing and...

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Testing and research conducted by or with funds... Categories of Records § 20.105 Testing and research conducted by or with funds provided by the Food and DrugAdministration. (a) Any list that may be prepared by the Food and DrugAdministration of testing and...

... HUMAN SERVICES Food and DrugAdministration Memorandum of Understanding Between the Food and Drug..., and Food Nutrition Service AGENCY: Food and DrugAdministration, HHS. ACTION: Notice. SUMMARY: The... Food Nutrition Service. The purpose of the MOU is to provide a framework for the parties to...

Intravenously administered nanocarriers are widely studied to improve the delivery of various therapeutic agents. However, recent in vivo studies have demonstrated that intravenously administered nanocarriers that do not contain any drug may affect cardiovascular function. Here we provide an example where the drug and the nanocarrier both affect the same cardiovascular parameters following intravenous administration. The peptide ghrelin antagonist (GhA) increases arterial pressure, while thermally hydrocarbonized porous silicon nanoparticles (THCPSi) transiently decrease it, as assessed with radiotelemetry in conscious rats. As a result, intravenous administration of GhA-loaded THCPSi nanoparticles partially antagonized GhA activity: arterial pressure was not increased. When the cardiovascular effects of GhA were blocked with atenolol pretreatment, GhA-loaded nanoparticles reduced arterial pressure to similar extent as drug-free nanoparticles. These data indicate that the biological activity of a drug delivered within a nanocarrier may be obscured by the biological responses induced by the nanocarrier itself. PMID:24964293

.... Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of...- specific therapy offers hope that new medications or combinations of drugs may one day slow the...

Patients in paediatric intensive care units (PICU) often receive numerous medications by the parenteral route. Frequently two or more drugs are delivered simultaneously through the same line and the risk of physicochemical incompatibilities is thus important. The objectives of this study were 1) to identify prospectively the combinations of injectable drugs administered in the PICU of our university hospital and 2) to analyze them according to information found in the literature. The data were collected by a pharmacist over a 30-day period and classified in three categories: compatible, incompatible and undocumented. Nineteen patients were included in the study with a median age of 3.2 years. The mean number (+/- SD) of injectable drugs per patient and per day was 6.5 (+/- 2.8), for a total of 26 drugs and 7 solutes. 64 combinations of drugs were observed with 2 (31.3%), 3 (45.3%), 4 (10.9%) or 5 (12.5%) drugs. 81 drug-drug and 94 drug-solute combinations were recorded. Among these, 151 (86.3%) were compatible, 6 (3.4%) incompatible and 18 (10.3%) undocumented. The incompatibilities included furosemide (Lasix), a drug in alkaline solution and Vamina-Glucose, a total parenteral nutrition solution. No clinical consequences resulting from drug incompatibilities were shown in this study. We suggest that in vitro compatibility tests on standard drug combinations, as well as a training program for nurses on drug incompatibility problems would sensitively increase the security of parenteral drugadministration. PMID:11028261

Objective To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls. Design Cohort study of outpatients using administrative data. Setting 3 US Medicaid programmes. Participants Patients with schizophrenia treated with clozapine, haloperidol, risperidone, or thioridazine; a control group of patients with glaucoma; and a control group of patients with psoriasis. Main outcome measure Diagnosis of cardiac arrest or ventricular arrhythmia. Results Patients with treated schizophrenia had higher rates of cardiac arrest and ventricular arrhythmia than controls, with rate ratios ranging from 1.7 to 3.2. Overall, thioridazine was not associated with an increased risk compared with haloperidol (rate ratio 0.9, 95% confidence interval 0.7 to 1.2). However, thioridazine showed an increased risk of events at doses ⩾600 mg (2.6, 1.0 to 6.6; P=0.049) and a linear dose-response relation (P=0.038). Conclusions The increased risk of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia could be due to the disease or its treatment. Overall, the risk with thioridazine was no worse than that with haloperidol. Thioridazine may, however, have a higher risk at high doses, although this finding could be due to chance. To reduce cardiac risk, thioridazine should be prescribed at the lowest dose needed to obtain an optimal therapeutic effect. What is already known on this topicThioridazine seems to prolong the electrocardiographic QT interval more than haloperidolAlthough QT prolongation is used as a marker of arrhythmogenicity, it is unknown whether thioridazine is any worse than haloperidol with regard to cardiac safetyWhat this study addsPatients taking antipsychotic drugs had higher risks of cardiac events than control patients with glaucoma or psoriasisOverall, the risk of cardiac arrest and ventricular arrhythmia was not higher with thioridazine than haloperidolThioridazine may

The February 2013 Food and DrugAdministration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. PMID:24698029

In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the real-world constraints commonly existing for health programmes. We explore how the optimal programme is affected by a variety of policy objectives, budget constraints, and prevalence settings. We develop a model of HCV transmission and treatment amongst active IDUs, determine the optimal treatment programme strategy over 10 years for two baseline chronic HCV prevalence scenarios (30% and 45%), a range of maximum annual budgets (£50,000-300,000 per 1,000 IDUs), and a variety of objectives: minimising health service costs and health utility losses; minimising prevalence at 10 years; minimising health service costs and health utility losses with a final time prevalence target; minimising health service costs with a final time prevalence target but neglecting health utility losses. The largest programme allowed for a given budget is the programme which minimises both prevalence at 10 years, and HCV health utility loss and heath service costs, with higher budgets resulting in greater cost-effectiveness (measured by cost per QALY gained compared to no treatment). However, if the objective is to achieve a 20% relative prevalence reduction at 10 years, while minimising both health service costs and losses in health utility, the optimal treatment strategy is an immediate expansion of coverage over 5-8 years, and is less cost-effective. By contrast, if the objective is only to minimise costs to the health service while attaining the 20% prevalence reduction, the programme is deferred

In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the real-world constraints commonly existing for health programmes. We explore how the optimal programme is affected by a variety of policy objectives, budget constraints, and prevalence settings. We develop a model of HCV transmission and treatment amongst active IDUs, determine the optimal treatment programme strategy over 10 years for two baseline chronic HCV prevalence scenarios (30% and 45%), a range of maximum annual budgets (50,000–300,000 per 1,000 IDUs), and a variety of objectives: minimising health service costs and health utility losses; minimising prevalence at 10 years; minimising health service costs and health utility losses with a final time prevalence target; minimising health service costs with a final time prevalence target but neglecting health utility losses. The largest programme allowed for a given budget is the programme which minimises both prevalence at 10 years, and HCV health utility loss and heath service costs, with higher budgets resulting in greater cost-effectiveness (measured by cost per QALY gained compared to no treatment). However, if the objective is to achieve a 20% relative prevalence reduction at 10 years, while minimising both health service costs and losses in health utility, the optimal treatment strategy is an immediate expansion of coverage over 5–8 years, and is less cost-effective. By contrast, if the objective is only to minimise costs to the health service while attaining the 20% prevalence reduction, the programme is deferred

... BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products... include in the bioequivalence requirement a requirement for manufacturers to submit samples of each batch... and DrugAdministration and found to meet the bioequivalence requirement, unless the public...

... BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products... include in the bioequivalence requirement a requirement for manufacturers to submit samples of each batch... and DrugAdministration and found to meet the bioequivalence requirement, unless the public...

Background While evidence on implementation of medication safety strategies is increasing, reasons for selecting and relinquishing distinct strategies and details on implementation are typically not shared in published literature. Objective We aimed to collect and structure expert information resulting from implementing medication safety strategies to provide advice for decision-makers. Setting Medication safety experts with clinical expertise from thirteen hospitals throughout twelve European and North American countries shared their experience in workshop meetings, on-site-visits and remote structured interviews. Methods We performed an expert-based, in-depth assessment of implementation of best-practice strategies to improve drug prescribing and drugadministration. Main outcome measures Workflow, variability and recommended medication safety strategies in drug prescribing and drugadministration processes. Results According to the experts, institutions chose strategies that targeted process steps known to be particularly error-prone in the respective setting. Often, the selection was channeled by local constraints such as the e-health equipment and critically modulated by national context factors. In our study, the experts favored electronic prescribing with clinical decision support and medication reconciliation as most promising interventions. They agreed that self-assessment and introduction of medication safety boards were crucial to satisfy the setting-specific differences and foster successful implementation. Conclusion While general evidence for implementation of strategies to improve medication safety exists, successful selection and adaptation of a distinct strategy requires a thorough knowledge of the institute-specific constraints and an ongoing monitoring and adjustment of the implemented measures. PMID:26964781

Abstract Background: Data regarding Y-site compatibility of intravenous (IV) cloxacillin sodium with other drugs are scarce and incomplete. Objective: To establish the compatibility of IV cloxacillin with 89 injectable drugs during simulated Y-site administration. Methods: Cloxacillin sodium (10 mL, 100 mg/mL) was combined with 89 undiluted IV drugs (10 mL, each). Tests were duplicated and performed at room temperature. Visual evaluation and a light obscuration particle count test were performed on 1 of the 2 solutions immediately after mixing. The second mixture underwent visual evaluation after 15 minutes, 1 hour, and 4 hours, followed by a particle count test at 4 hours. Drugs were considered incompatible if the mixture precipitated or became turbid within the 4-hour period or exceeded the particle count limit allowed by Test 1.B of USP <788> initially or at 4 hours. Results: Of the 89 tested drugs, 64 were compatible for up to 4 hours. The remaining 25 drugs were incompatible. Of these incompatible drugs, 16 were identified visually, and 9 were identified by the light obscuration particle count test. Conclusions: Sixty-four IV drugs were found to be compatible with cloxacillin via simulated Y-site, whereas 25 drugs were found to be incompatible with the antibiotic. The light obscuration particle count test should be used to complement visual evaluation when samples do not precipitate immediately. PMID:26405311

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Studies and reports prepared by or with funds provided by the Food and DrugAdministration. 20.106 Section 20.106 Food and Drugs FOOD AND DRUG... Categories of Records § 20.106 Studies and reports prepared by or with funds provided by the Food and...

... HUMAN SERVICES Food and DrugAdministration Cooperative Agreement To Support Regulatory Research Related...) announces its intention to accept and consider a single source application for award of a cooperative... accomplishment of these PDUFA V commitments. FDA is therefore seeking to establish a cooperative agreement...

...The Food and DrugAdministration (FDA) is announcing the availability of a guidance entitled ``Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by Clinical Investigators.'' This guidance is intended to assist clinical investigators, industry, and FDA staff in interpreting and complying with the regulations governing financial disclosure by clinical......

...The Food and DrugAdministration (FDA) is announcing the availability of the draft guidance entitled ``Highly Multiplexed Microbiological/Medical Countermeasure In Vitro Nucleic Acid Based Diagnostic Devices.'' This draft guidance is to provide industry and Agency staff with recommendations for studies to establish the analytical and clinical performance of highly multiplexed......

... violate a ban or restriction of the U.S. Food and DrugAdministration (FDA) pertaining to such products. If FDA bans or restricts the use of any ingredient in such a way that further manufacture of a product in accordance with its formula would violate the ban or restriction, then the manufacturer...

This handbook is for administrators of programs in higher education settings which deal with alcohol and other drug (AOD) related problems. Chapter 1, "Defining the Problem, Issues, and Trends" examines the problem from various perspectives and presents the latest statistics on the extent of AOD use on campuses, specific problems affecting…

...The Food and DrugAdministration (FDA or we) is announcing two public meetings to discuss two proposed rules aimed at strengthening assurances that imported food meets the same safety standards as food produced domestically. The Foreign Supplier Verification Programs (FSVP) proposal establishes requirements for importers to verify that their foreign suppliers are implementing the modern,......

...The Food and DrugAdministration (FDA) Cincinnati District, in cosponsorship with Xavier University, is announcing a public conference entitled ``FDA/Xavier University Global Outsourcing Conference.'' This public conference for the pharmaceutical industry is in direct alignment with the ``FDA Strategic Priorities 2011-2015,'' and includes presentations from key FDA officials, global......

...The Food and DrugAdministration (FDA) Cincinnati District, in cosponsorship with Xavier University, is announcing a public conference entitled ``FDA/Xavier University Global Outsourcing Conference.'' This 2.5-day public conference for the pharmaceutical industry is in direct alignment with the ``FDA Strategic Priorities 2011-2015,'' and includes presentations from key FDA officials, global......

... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE... of the selection process. (f) The railroad must randomly select a sufficient number of covered... objective, neutral criteria which ensures that every covered employee has a substantially equal...

... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE... of the selection process. (f) The railroad must randomly select a sufficient number of covered... objective, neutral criteria which ensures that every covered employee has a substantially equal...

...The Food and DrugAdministration (FDA) is announcing the availability of the draft guidance document entitled ``Draft Guidance for Industry and FDA Staff: Recommendations for Labeling Medical Products To Inform Users That the Product or Product Container Is Not Made With Natural Rubber Latex.'' The purpose of this draft guidance is to make recommendations on the appropriate language to include......

The activities within the NCL represent a formal scientific interaction of three Federal agencies: National Cancer Institute and U.S. Food and DrugAdministration (FDA) of the Department of Health and Human Services, and National Institute of Standards and Technology (NIST) of the Department of Commerce.

... Food and DrugAdministration and the International Anesthesia Research Society for the Safety of Key... memorandum of understanding (MOU) between FDA and the International Anesthesia Research Society (IARS)....

Objective There is currently a gap in on-site drug of abuse monitoring. Current detection methods involve invasive sampling of blood and urine specimens, or collection of oral fluid, followed by qualitative screening tests using immunochromatographic cartridges. While remote laboratories then may provide confirmation and quantitative assessment of a presumptive positive, this instrumentation is expensive and decoupled from the initial sampling making the current drug-screening program inefficient and costly. The authors applied a noninvasive oral fluid sampling approach integrated with the in-development chip-based Programmable Bio-Nano-Chip (p-BNC) platform for the detection of drugs of abuse. Method The p-BNC assay methodology was applied for the detection of tetrahydrocannabinol, morphine, amphetamine, methamphetamine, cocaine, methadone and benzodiazepines, initially using spiked buffered samples and, ultimately, using oral fluid specimen collected from consented volunteers. Results Rapid (~10 minutes), sensitive detection (~ng/ml) and quantitation of 12 drugs of abuse was demonstrated on the p-BNC platform. Furthermore, the system provided visibility to time-course of select drug and metabolite profiles in oral fluids; for the drug cocaine, three regions of slope were observed that, when combined with concentration measurements from this and prior impairment studies, information about cocaine-induced impairment may be revealed. Conclusions This chip-based p-BNC detection modality has significant potential to be used in the future by law enforcement officers for roadside drug testing and to serve a variety of other settings, including outpatient and inpatient drug rehabilitation centers, emergency rooms, prisons, schools, and in the workplace. PMID:26048639

The emergence and spread of antimalarial resistance has been a major liability for malaria control. The spread of chloroquine-resistant Plasmodium falciparum strains had catastrophic consequences for people in malaria-endemic regions, particularly in sub-Saharan Africa. The recent emergence of artemisinin-resistant P. falciparum strains is of highest concern. Current efforts to contain artemisinin resistance have yet to show success. In the absence of more promising plans, it has been suggested to eliminate falciparum malaria from foci of artemisinin resistance using a multipronged approach, including mass drugadministrations. The use of mass drugadministrations is controversial as it increases drug pressure. Based on current knowledge it is difficult to conceptualize how targeted malaria elimination could contribute to artemisinin resistance, provided a full treatment course is ensured. PMID:25831482

Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and DrugAdministration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development. PMID:27194113

Cigarette smoking is ubiquitous among illicit drug users. Some have speculated that this may be partially due to similarities in the route of administration. However, research examining the relationship between cigarette smoking and routes of administration of illicit drugs is limited. To address this gap, we investigated sociodemographic and drug use factors associated with cigarette smoking among cocaine and heroin users in the Baltimore, Maryland community (N=576). Regular and heavy cigarette smokers were more likely to be White, have a history of a prior marriage, and have a lower education level. Regular smoking of marijuana and crack was associated with cigarette smoking, but not heavy cigarette smoking. Injection use was more common among heavy cigarette smokers. In particular, regular cigarette smokers were more likely to have a lifetime history of regularly injecting heroin. Optimal prevention and treatment outcomes can only occur through a comprehensive understanding of the interrelations between different substances of abuse. PMID:22305644

The sale of consumer products over the Internet has grown rapidly, including the sale of drugs. While the growth in online drug sales by reputable pharmacies is a trend that may provide benefits to consumers, online drug sales also present risks to purchasers and some unique challenges to regulators, law enforcement officials and policy makers. The Food and DrugAdministration (FDA or the Agency) is concerned about the public health implications of Internet drug sales, and we are responding to these concerns as part of our overall goal of developing and implementing risk-based strategies to protect public health and safety. Although other products regulated by the Agency, such as medical devices, medical test products, foods, dietary supplements and animal drugs also are sold online, this paper focuses on online drug sales. We discuss the advantages and risks of online drug sales, outline FDA's authority and enforcement activities in this area, and describe new initiatives we are taking to better respond to the regulatory challenges we face. PMID:11720945

The sale of consumer products over the Internet has grown rapidly, including the sale of drugs. While the growth in online drug sales by reputable pharmacies is a trend that may provide benefits to consumers, online drug sales also present risks to purchasers and some unique challenges to regulators, law enforcement officials and policy makers. The Food and DrugAdministration (FDA or the Agency) is concerned about the public health implications of Internet drug sales, and we are responding to these concerns as part of our overall goal of developing and implementing risk-based strategies to protect public health and safety. Although other products regulated by the Agency, such as medical devices, medical test products, foods, dietary supplements and animal drugs also are sold online, this paper focuses on online drug sales. We discuss the advantages and risks of online drug sales, outline FDA's authority and enforcement activities in this area, and describe new initiatives we are taking to better respond to the regulatory challenges we face. PMID:11720945

Aim: Aim of this study is to determine the levels of knowledge related with drugadministration and drugadministration errors of nurses who care for pediatric patients. Material and Methods: The study data were obtained from the nurses who were working in the departments of pediatrics in two education and research hospitals in the province of İstanbul and who accepted to participate in the study. The questionnaire form of the study was established by the investigators in accordance with the experiences and literature information. A total of 31 questions related with drug preparation, calculation and administration together with the general working properties of the individual were filled out by face to face interview. The data were evaluated using percent and chi-square tests. The study was initiated after ethics committee approval was obtained from Şişli Hamidiye Etfal Education and Research Hospital (365/2013). Results: The study was conducted with 98 nurses who accepted the questionnaire. The education levels of the participants were as follows: undergraduate (48%), high school (32.7%), associate degree (12.2%), master’s degree (6.1%) and postgraduate (1%). It was found that 88.8% of the participants worked in a patient-centered fashion and 11.2% worked in a work-centered fashion. The frequency of interruption/distraction during preparation of treatment was found to be 92.9%. It was found that the frequency of checking by two people during preparation or administration of high risk drugs was 64.3% and the conditions under which drugs should be kept were found to known correctly with a rate of 76.5%. It was found that undergraduate healthcare workers were more successful in converting units (p= 0.000). It was found that powder weight of drugs was considered with a rate of 85.7% in calculation. Conclusions: Conclusively, it was found that nurses who worked in pediatric wards did not receive a standard education in terms of drugadministration and preparation

Background The analysis of electronic health records for an automated detection of adverse drug reactions is an approach to solve the problems that arise from traditional methods like spontaneous reporting or manual chart review. Algorithms addressing this task should be modeled on the criteria for a standardized case causality assessment defined by the World Health Organization. One of these criteria is the temporal relationship between drug intake and the occurrence of a reaction or a laboratory test abnormality. Appropriate data that would allow for developing or validating related algorithms is not publicly available, though. Methods In order to provide such data, retrospective routine data of drugadministrations and temporally corresponding laboratory observations from a university clinic were extracted, transformed and evaluated by experts in terms of a reasonable time relationship between drugadministration and lab value alteration. Result The result is a data corpus of 400 episodes of normalized laboratory parameter values in temporal context with drugadministrations. Each episode has been manually classified whether it contains data that might indicate a temporal correlation between the drugadministration and the change of the lab value course, whether such a change is not observable or whether a decision between those two options is not possible due to the data. In addition, each episode has been assigned a concordance value which indicates how difficult it is to assess. This is the first open data corpus of a computable ground truth of temporal correlations between drugadministration and lab value alterations. Discussion The main purpose of this data corpus is the provision of data for further research and the provision of a ground truth which allows for comparing the outcome of other assessments of this data with the outcome of assessments made by human experts. It can serve as a contribution towards systematic, computerized ADR detection in

Aim: This pilot study investigated what alcohol prevention benefits could be achieved by a harm reduction focused school drug education intervention that addressed all drug use, both licit and illicit. Method: The study population comprised a cohort of 225 students in three intervention secondary schools and 93 students in a matched control school…

According to the World Health Organization, one of the criteria for the standardized assessment of case causality in adverse drug reactions is the temporal relationship between the intake of a drug and the occurrence of a reaction or a laboratory test abnormality. This article presents and describes an algorithm for the detection of a reasonable temporal correlation between the administration of a drug and the alteration of a laboratory value course. The algorithm is designed to process normalized lab values and is therefore universally applicable. It has a sensitivity of 0.932 for the detection of lab value courses that show changes in temporal correlation with the administration of a drug and it has a specificity of 0.967 for the detection of lab value courses that show no changes. Therefore, the algorithm is appropriate to screen the data of electronic health records and to support human experts in revealing adverse drug reactions. A reference implementation in Python programming language is available. PMID:27042396

According to the World Health Organization, one of the criteria for the standardized assessment of case causality in adverse drug reactions is the temporal relationship between the intake of a drug and the occurrence of a reaction or a laboratory test abnormality. This article presents and describes an algorithm for the detection of a reasonable temporal correlation between the administration of a drug and the alteration of a laboratory value course. The algorithm is designed to process normalized lab values and is therefore universally applicable. It has a sensitivity of 0.932 for the detection of lab value courses that show changes in temporal correlation with the administration of a drug and it has a specificity of 0.967 for the detection of lab value courses that show no changes. Therefore, the algorithm is appropriate to screen the data of electronic health records and to support human experts in revealing adverse drug reactions. A reference implementation in Python programming language is available. PMID:27042396

The present study established a novel mouse model of a runway drug self-administration in our laboratory. The operant runway apparatus consisted of three long runways arranged in a zig-zag manner. The methodology consisted of six distinct phases: habituation, preconditioning, conditioning, post-conditioning, extinction and reinstatement. The effects of saline were compared with escalating doses of either ethanol (0.5-4.0 g/kg, i.p), heroin (5-40 mg/kg, i.p), or nicotine (0.1-0.5mg/kg, i.p) administered in the goal box during the conditioning phase (day 1 to day 5). A significant decrease in the time of trained (conditioned) mice to reach the goal box confirmed the subjects' motivation to seek those drugs on day 6 (expression). The mice were then subjected to non-rewarded extinction trials for 5 days over which run times were significantly increased. After 5 days of abstinence, a priming dose of ethanol or heroin (1/5th of maximum dose used in conditioning) significantly reinstated the drug-seeking behavior. These results suggest that the modified runway model can serve as a powerful behavioral tool for the study of the behavioral and neurobiological bases of drug self-administration and, as such, is appropriate simple but powerful tool for investigating the drug-seeking behavior of laboratory mice. PMID:26902717

The present study established a novel mouse model of a runway drug self-administration in our laboratory. The operant runway apparatus consisted of three long runways arranged in a zig-zag manner. The methodology consisted of six distinct phases: habituation, preconditioning, conditioning, post-conditioning, extinction and reinstatement. The effects of saline were compared with escalating doses of either ethanol (0.5–4.0 g/kg, i.p), heroin (5–40 mg/kg, i.p), or nicotine (0.1–0.5mg/kg, i.p) administered in the goal box during the conditioning phase (day 1 to day 5). A significant decrease in the time of trained (conditioned) mice to reach the goal box confirmed the subjects’ motivation to seek those drugs on day 6 (expression). The mice were then subjected to non-rewarded extinction trials for 5 days over which run times were significantly increased. After 5 days of abstinence, a priming dose of ethanol or heroin (1/5th of maximum dose used in conditioning) significantly reinstated the drug-seeking behavior. These results suggest that the modified runway model can serve as a powerful behavioral tool for the study of the behavioral and neurobiological bases of drug self-administration and, as such, is appropriate simple but powerful tool for investigating the drug-seeking behavior of laboratory mice. PMID:26902717

Introduction/background: Zolpidem is a sedative-hypnotic widely prescribed in the United States. Recently, the US Food and DrugAdministration (FDA) issued a drug safety communication regarding its dosing in women. Objective: To compare compliance with FDA-approved dosing for zolpidem in women before and after a drug safety communication, and to evaluate compliance based on pharmacy location and prescriber type. Method: This was a retrospective, observational cohort study. New prescriptions for Ambien, Ambien CR, Edluar, or Zolpimist or their respective generics dispensed from Kerr Drug pharmacies in North Carolina to women 18–64 years of age between April and September of 2012 (“before” cohort) or April and September of 2013 (“after” cohort) were included. χ2 tests were conducted to assess overall compliance, as well as compliance based on location (urban or rural) and prescriber type (physician or midlevel), with FDA-approved dosing for zolpidem. Trends in total prescription volume and total zolpidem prescription volume for all Kerr Drug pharmacies over the study period were also described. Results: A total of 14,156 prescriptions for zolpidem were included in the primary analysis. Sixteen percent of prescriptions dispensed were in compliance with FDA recommendations following the FDA alert. A statistically significant increase was observed in compliance with FDA-approved dosing for zolpidem (odds ratio = 1.49; 95% CI, 1.35–1.65; P < .0001) postdrug safety communication. Significant increases in compliance were also observed in the post-FDA communication subgroups based on location and prescriber type, though no subgroup was found to be significantly more compliant than another. Conclusions: The release of a drug safety communication by the FDA resulted in a statistically significant increase in proper dosing of zolpidem in women. Further research is needed in order to determine the impact of FDA alerts on prescribing patterns and the reasons for

Prompted by approval in 1997 of troglitazone and bromfenac, two drugs that promptly began to show serious and sometimes fatal liver toxicity, we began at the Food and DrugAdministration (FDA) a series of annual conferences in 1999 to consider issues of drug-induced liver injury (DILI). First inviting reviewers of new drug applications we opened the audiences in 2001 to pharmaceutical industry and academic consultants to industry and FDA, and slides shown at the meetings were posted on the internet to be available at the website of the American Association for the Study of Liver Diseases (AASLD)-go to ( http://www.aasld.org/dili/Pages/default.aspx ). Observations by Dr. Hyman J. Zimmerman that "drug-induced hepatocellular jaundice is a serious lesion" with possible mortality formed a basis for developing a computer program to plot peak serum values for alanine aminotransferase (ALT) and total bilirubin (TBL) in an x-y log-log graph for all subjects enrolled in clinical trials. This program had the capability to show the time course of all liver tests for individuals who had both hepatocellular injury and reduced whole liver function, plus clinical narratives to diagnose the severity and most likely cause of the abnormalities. We called the program eDISH (for evaluation of Drug-Induced Serious Hepatotoxicity), and began in 2004 to use it to assess DILI in clinical trial subjects. From 2008, comments made by the presenters at the conferences about their slides and ensuing discussions have been added to the website. All this has raised awareness of the problem, and since 1997, the FDA has not had to withdraw a single drug because of post-marketing hepatotoxicity. Many issues still remain to be resolved; among the most controversial is the best method to estimate likelihood that a given liver injury was actually caused by the drug in question. On November 9, 2012, a workshop was convened to discuss the best practices for the assessment of drug-induced liver injury

Tramadol hydrochloride (TrHC) is a synthetic analgesic drug exhibiting opioid and non-opioid properties, acting mainly on the central nervous system. It has been mostly used to treat pain, although its use to treat anxiety and depression has also been documented. These properties arise from the fact that they inhibit serotonin (5-HT) reuptake augmenting 5-HT concentration on the synaptic cleft. Despite this, TrHC has also been described to have several side effects which are mainly due to its fast metabolization and excretion which in turn requires multiple doses per day. To surpass this limitation, new pharmaceutical formulations are being developed intending the protection, target and sustained delivery as well as a reduction on daily dose aiming a reduction on the side effects. In the present work we have revised the efficacy, safety, biological and adverse effects of TrHC, and the added value of developing a novel drug delivery system for topical administration. PMID:25776506

...The Food and DrugAdministration (FDA) is establishing a public docket for information pertaining to FDA's implementation of the provisions of the Food and DrugAdministration Safety and Innovation Act (FDASIA) related to medical gases. This action is intended to ensure that information submitted to FDA on the implementation of the medical gas provisions of FDASIA is available to all......

... HUMAN SERVICES Food and DrugAdministration The 13th Annual Food and DrugAdministration-Orange County...-sponsored with the Orange County Regulatory Affairs Discussion Group (OCRA). The conference is intended to...-608-4417; or Orange County Regulatory Affairs Discussion Group ] (OCRA), Attention to Detail,...

... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and DrugAdministration The 15th Annual Food and DrugAdministration--Orange County... announcing the following conference: The 15th Annual Educational Conference cosponsored with the...

...'' that appeared in the Federal Register of August 1, 2011 (76 FR 45818). In that document, FDA announced.... Background In the Federal Register of August 1, 2011 (76 FR 45818), FDA published a notice with a 78-day... HUMAN SERVICES Food and DrugAdministration Burden of Food and DrugAdministration Food...

The US Food and DrugAdministration (FDA) Web site includes a vast amount of information, but it can be difficult to navigate. Despite frequently asked question (FAQ)-type pages within the Web site, it may not be easy for first-time users to find drug information. This article presents some examples of common questions, provides the locations of the answers on the FDA Web site, and gives a brief description of some of the many resources the FDA provides for health care professionals. Additionally, a newer project being undertaken by the FDA, Snapshot, is introduced. PMID:27621506

Our laboratory has developed an integrative approach to study the molecular changes and behavioral effects of drugadministration consisting of a combination of quantitative real-time reverse transcription polymerase chain reaction, RNA isolation and differential display, in situ hybridization, place preference conditioning and high-performance liquid chromatography. Although the techniques are not novel, this multi-systems approach allows for the examination of gene expression changes following the administration of drugs of abuse such as cocaine, and allows for an analysis of behavior and neurochemistry of gene knockout mice. As a result of this combination of techniques, we have been able to determine the expression, location and function of the CD81 protein. Specifically, CD81 was induced exclusively in the nucleus accumbens by cocaine treatment. Subsequent behavioral testing of CD81 knockout mice revealed these mice displayed altered sensitivity to cocaine. PMID:12113778

The World Health Organization recommends that before lymphatic filariasis elimination in an area can be confirmed, an additional survey should be performed at least 5 years after stopping mass drugadministration. The current study aimed to determine the status of lymphatic filariasis 5 years after cessation ofthe mass drugadministration in 3 sentinel Egyptian villages in Menoufiya Governorate. The rapid immunochromatographic card test (ICT) and a new commercial antibody detection kit (CELISA®) were used. All 1321 primary-school children aged 6-7 years old were ICT negative but 27 children were antibody positive. All households surveyed in one village with the highest antibody prevalence were ICT negative, indicating an absence of lymphatic filariasis. The CELISA antibody kit needs more standardization and development to be useful under field conditions. We conclude that lymphatic filariasis is no longer a public health problem in these villages and other villages with similar epidemiological conditions. PMID:24952286

There is a lack of research and consensus on the long-term risks of occupational exposure to monoclonal antibodies. There is, however, some risk to health professionals who are involved in their preparation and administration. This article discusses the use of closed-system drug transfer devices to minimise exposure, and touches on the importance of aseptic techniques, personal protective equipment, and appropriate education and training for health professionals. PMID:26946648

On July 24, 2014, the Food and DrugAdministration (FDA) held an open forum to review proposed changes to the Nutrition Facts Label and to allow for public comment on these changes. Lisa Gutekunst, MSEd, RD, CSR, CDN, Chair of the National Kidney Foundation Council on Renal Nutrition, lobbied the FDA to add phosphorus to the Nutrition Facts Label. This is her address to the FDA. PMID:25443545

... the Federal Food, Drug, and Cosmetic Act''; Availability AGENCY: Food and DrugAdministration, HHS... Products as Used in Section 904(e) of the Federal Food, Drug, and Cosmetic Act.'' This draft guidance... Cosmetic Act.'' This draft guidance, when finalized, will discuss the meaning of the term ``harmful...

Background Lymphatic filariasis (LF) caused by Wuchereria bancrofti is present at high prevalence in some parts of Papua New Guinea. However, there has been no rigorous data-based representative assessment of nationwide prevalence of LF. The LF programme has been daunted by the scope of the problem, and progress on mass drugadministration (MDA) has been slow and lacking in resources. Methods A systematic literature review identified LF surveys in Papua New Guinea between 1980 and 2011. Results were extracted by location, time period and test used (blood slide, immunochromatographic test (ICT) or Og4C3 ELISA) and combined by district. Three criteria schemes based on the Global Programme to Eliminate Lymphatic Filariasis guidelines, with modifications, were developed to classify and prioritize districts by prevalence level. Results of repeated surveys in the same sites were used to investigate the impact of MDA on LF prevalence over the time period. Results There were 312 distinct survey sites identified in 80 of the 89 districts over the 31-year period. The overall LF prevalence in the sites tested was estimated at 18.5 to 27.5% by blood slide for microfilariae (Mf), 10.1% to 12.9% by ICT and 45.4% to 48.8% by Og4C3. Biases in site selection towards areas with LF, and change in type of assay used, affected the prevalence estimates, but overall decline in prevalence over the time period was observed. Depending on the criteria used, 34 to 36 districts (population 2.7 to 2.9 million) were classed as high endemic (≥5% prevalence), 15 to 25 districts (1.7 to 1.9 million) as low endemic (<5%) and 20 to 31 (1.3 to 2.2 million) as non-endemic. Nine districts (0.7 million) had no information. The strong impact of MDA, especially on microfilaria (Mf) prevalence, was noted in sites with repeat surveys. Conclusions This analytical review of past surveys of LF in Papua New Guinea enables better estimation of the national burden, identifies gaps in knowledge, quantifies and

Staphylococcal enterotoxin C2 (SEC2) is a classical superantigen (SAg), which can tremendously activate T lymphocytes at very low dosage, thus exerting its powerful antitumor activity. As an intravenous protein drug and a bacterial toxin, SEC2 has some limitations including poor patient compliance and toxic side effects. In this research, we devoted our attention to studying the antitumor activity and toxicity of SEC2 as a potential oral administration protein drug. We proved that His-tagged SEC2 (SEC2-His) could undergo facilitated transcytosis on human colon adenocarcinoma (Caco-2) cells and SEC2-His was detected in the blood of rats after oral administration. Furthermore, oral SEC2-His caused massive cytokine release and immune cell enrichment around tumor tissue, leading to inhibition of tumor growth in vivo. Meanwhile, although SEC2-His was dosed up to 32 mg/kg in mice, no significant toxicity was observed. These data showed that SEC2 can cross the intestinal epithelium in an immunologically integral form, maintaining antitumor activity but with reduced systemic toxicity. Therefore, these results may have implications for developing SEC2 as an oral administration protein drug. PMID:27322320

Staphylococcal enterotoxin C2 (SEC2) is a classical superantigen (SAg), which can tremendously activate T lymphocytes at very low dosage, thus exerting its powerful antitumor activity. As an intravenous protein drug and a bacterial toxin, SEC2 has some limitations including poor patient compliance and toxic side effects. In this research, we devoted our attention to studying the antitumor activity and toxicity of SEC2 as a potential oral administration protein drug. We proved that His-tagged SEC2 (SEC2-His) could undergo facilitated transcytosis on human colon adenocarcinoma (Caco-2) cells and SEC2-His was detected in the blood of rats after oral administration. Furthermore, oral SEC2-His caused massive cytokine release and immune cell enrichment around tumor tissue, leading to inhibition of tumor growth in vivo. Meanwhile, although SEC2-His was dosed up to 32 mg/kg in mice, no significant toxicity was observed. These data showed that SEC2 can cross the intestinal epithelium in an immunologically integral form, maintaining antitumor activity but with reduced systemic toxicity. Therefore, these results may have implications for developing SEC2 as an oral administration protein drug. PMID:27322320

Recently, evidence has emerged from an unusual form of mass drugadministration practised among detainees held at US Naval Station Guantánamo Bay, Cuba ('Guantánamo'), ostensibly as a public health measure. Mefloquine, an antimalarial drug originally developed by the US military, whose use is associated with a range of severe neuropsychiatric adverse effects, was administered at treatment doses to detainees immediately upon their arrival at Guantánamo, prior to laboratory testing for malaria and irrespective of symptoms of disease. In this analysis, the history of mefloquine's development is reviewed and the indications for its administration at treatment doses are discussed. The stated rationale for the use of mefloquine among Guantánamo detainees is then evaluated in the context of accepted forms of population-based malaria control. It is concluded that there was no plausible public health indication for the use of mefloquine at Guantánamo and that based on prevailing standards of care, the clinical indications for its use are decidedly unclear. This analysis suggests the troubling possibility that the use of mefloquine at Guantánamo may have been motivated in part by knowledge of the drug's adverse effects, and points to a critical need for further investigation to resolve unanswered questions regarding the drug's potentially inappropriate use. PMID:22882560

A study was conducted on 19 community volunteers and the training module they underwent is presented. The subjects were given 7 days in-training with the objectives of imparting knowledge ana skill to identify and motivate alcohol and drug dependent person, to motivate them and their family to seek treatment to provide social support to them and to organise prevention programmes in the community. Their knowledge, skills and attitudes have shown significant improvement and change as a result to training. Extraversion was found to be significantly related to change in all the above variables, psychoticism was related to attitude and self-esteem was related to improvement in skills. Need for under taking further research in this area is also emphasized. PMID:21584078

A study was conducted on 19 community volunteers and the training module they underwent is presented. The subjects were given 7 days in-training with the objectives of imparting knowledge ana skill to identify and motivate alcohol and drug dependent person, to motivate them and their family to seek treatment to provide social support to them and to organise prevention programmes in the community. Their knowledge, skills and attitudes have shown significant improvement and change as a result to training. Extraversion was found to be significantly related to change in all the above variables, psychoticism was related to attitude and self-esteem was related to improvement in skills. Need for under taking further research in this area is also emphasized. PMID:21584078

Purpose Commonly prescribed medications produce QT-prolongation and are associated with torsades de pointes in non-acutely ill patients. We examined patterns of QT-prolonging drug use in critically ill individuals. Methods An administrative critical care database was utilized to identify patients receiving drugs associated with QT-interval prolongation or torsades de pointes for ≥24 hours. Results Data from 212,016 individuals collected over a 63-month period was examined to identify 6,125 patients (2.9%) receiving QT-interval prolonging drugs. These individuals had a mean (±SE) age of 63.0 (±0.2) years, were predominately male (55.4%) and Caucasian (84.4%), and were exposed to QT-interval prolonging agents for a mean (±SE) 53.1 (±0.4) % of their ICU length of stay. Respiratory and cardiovascular illnesses were the most common reasons for ICU admission (17.2%, 12.0%, respectively). The most frequently administered agents were Amiodarone (23.5%), Haloperidol (19.8%), and Levofloxacin (19.7%); no other single agent accounted for more than 10% of QT-interval prolonging drugs prescribed. Coadministration of QT-prolonging drugs occurred in 1,139 patients (18.6%). These patients had higher ICU mortality rate and longer ICU lengths of stay, compared to patients not receiving coadministered drugs (p<0.001 for both). For patients receiving coadministered drugs, overlap occurred for 71.4 (±0.8) % of the time that the drugs were given. Amiodarone coadministration with antibiotics, Haloperidol coadministration with antibiotics, and Haloperidol coadministration with Amiodarone, comprised 15.2%, 13.7%, and 9.4%, of all coadministered agents, respectively. Conclusions QT-prolonging drugs were used in a minority of critically ill patients. Prospective evaluation in the ICU environment is necessary to determine whether administration of these agents is associated with adverse cardiac events comparable to those reported in ambulatory patients. PMID:18693297

The development and optimization of many new drug therapies requires long-term local delivery with controlled, but variable dosage. Current methods for chronic drug delivery have limited utility because they either cannot deliver drugs locally to a specific organ or tissue, do not permit changes in delivery rate in situ, or cannot be used in clinical trials in an untethered, wearable configuration. Here, we describe a small, self-contained system for liquid-phase drug delivery. This system enables studies lasting several months and infusion rates can be programmed and modified remotely. A commercial miniature pump is integrated with microfabricated components to generate ultralow flow rates and stroke volumes. Solutions are delivered in pulses as small as 370 nL, with pulses delivered at any interval of 1 min or longer. A unique feature of the system is the ability to infuse and immediately withdraw liquid, resulting in zero net volume transfer while compounds are exchanged by mixing and diffusion with endogenous fluid. We present in vitro results demonstrating repeatability of the delivered pulse volume for nearly 3 months. Furthermore, we present in vivo results in an otology application, infusing into the cochlea of a guinea pig a glutamate receptor antagonist, which causes localized and reversible changes in auditory sensitivity. PMID:19089621

Drug prescription and administration processes strongly impact on the occurrence of risks in medical settings for they can be sources of adverse drug events (ADEs). A properly engineered use of information and communication technologies has proven to be a promising approach to reduce these risks. In this study, we propose PHARMA, a web information system which supports healthcare staff in the secure cooperative execution of drug prescription, transcription and registration tasks. PHARMA allows the easy sharing and management of documents containing drug-related information (i.e., drug prescriptions, medical reports, screening), which is often inconsistent and scattered across different information systems and heterogeneous organization domains (e.g., departments, other hospital facilities). PHARMA enables users to access such information in a consistent and secure way, through the adoption of REST and web-oriented design paradigms and protocols. We describe the implementation of the PHARMA prototype, and we discuss the results of the usability evaluation that we carried out with the staff of a hospital in Florence, Italy. PMID:24107986

ABSTRACT Zebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drugadministration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAFV600E inhibitor, Vemurafenib, in adult zebrafish harboring BRAFV600E melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1) and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases. PMID:27482819

Background Adverse drug events, the unintended and harmful effects of medications, are important outcome measures in health services research. Yet no universally accepted set of International Classification of Diseases (ICD) revision 10 codes or coding algorithms exists to ensure their consistent identification in administrative data. Our objective was to synthesize a comprehensive set of ICD-10 codes used to identify adverse drug events. Methods We developed a systematic search strategy and applied it to five electronic reference databases. We searched relevant medical journals, conference proceedings, electronic grey literature and bibliographies of relevant studies, and contacted content experts for unpublished studies. One author reviewed the titles and abstracts for inclusion and exclusion criteria. Two authors reviewed eligible full-text articles and abstracted data in duplicate. Data were synthesized in a qualitative manner. Results Of 4241 titles identified, 41 were included. We found a total of 827 ICD-10 codes that have been used in the medical literature to identify adverse drug events. The median number of codes used to search for adverse drug events was 190 (IQR 156–289) with a large degree of variability between studies in the numbers and types of codes used. Authors commonly used external injury (Y40.0–59.9) and disease manifestation codes. Only two papers reported on the sensitivity of their code set. Conclusions Substantial variability exists in the methods used to identify adverse drug events in administrative data. Our work may serve as a point of reference for future research and consensus building in this area. PMID:24222671

The "manometric" way of considering the complex management of high blood pressure (HBP) must remain ancient history. The huge therapeutical armamentarium existing nowadays allows us to select the drug/s most appropriate for the comorbidities/particularities of each case. The BP level target, unanimously considered a very important element of HBP management, must not be the only one. The so-called pleiotropic effects of the different classes of antihypertensive drugs must always influence our way of thinking. Another important possibility to improve the therapeutical efficacy of the antihypertensive treatment is chronotherapy. The aim of the present study is to demonstrate the possibility of some benefic effects by imposing, by chronotherapy, a "normal" "dipping" status of the BP values. Among the surrogate end-points that can be used to demonstrate the benefits of this kind of HBP management we chose the structural and functional cardiac parameters, echocardiographically determined--using the criteria of the American Society of Echocardiography. We studied the evolution of these parameters of the left ventricle (LV) and we have evaluated them after 3 months of once-a-day morning (at awakening) administration, and respectively after 3 months of once-a-day administration in the evening (at bedtime) of: Prestarium (perindopril) cp 10 mg Tarka (cp 180 mg verapamil hydrochloride/2 mg trandolapril) Norvasc (amlodipine besilat) cp 10 mg as monotherapy, in 60 patients. We studied the anatomical parameters of the left ventricle (dimensions measured enddiastolically: the thickness of the interventricular septum, the thickness of the posterior wall, the internal diameter of the LV), the LV mass (which has a cutedge value for hypertrophy of the LV-LVH--of 134 g/m2 for men and 110 g/m2 for women) and the functional parameters, systolic as diastolic of the LV. We noticed a statistically significant reduction (p < 0.05) in all the 3 subgroups, of the functional parameters, these

The present study aimed to formulate dexamethasone (DXM), a poorly soluble drug, into nanostructured lipid carriers (NLCs) for intravenous administration by employing a phospholipids complex. Initially, dexamethasone-phospholipids complex (DPC) was synthesized and characterized. Subsequently, DPC was entrapped into NLCs and the process was optimized using spherical symmetric design-surface response methodology. Then, the characteristics, in vitro release behavior and physical stability of the optimized DPC loaded NLCs (DPC-NLCs) were investigated. Comparison between DPC-NLCs and free DXM loaded NLCs was also conducted in the aspects of particle size, entrapment efficiency (EE), drug loading efficiency (DL), initial release and zeta potential. The results showed the optimized DPC-NLCs were prepared with an average size of 189.33 ± 0.58 nm, EE of 89.82 ± 1.64%, DL of 2.13 ± 0.13% and good physical stability for 30 days. In vitro release profile exhibited an initial burst release followed by a prolonged release. Compared with free DXM loaded NLCs, the EE and DL of DPC-NLCs were higher while the initial release was lower. These advantages of DPC-NLCs proved the phospholipids complex played an essential role in NLCs formulation and showed the potential for intravenous administration of poorly soluble drugs. PMID:21222507

Background In spite of enhanced control efforts, malaria remains a major public health problem causing close to a million deaths annually. With support from several donors, large amounts of artemisinin-based combination therapy (ACT) are being deployed in endemic countries raising safety concerns as little is known about the use of ACT in several of the settings where they are deployed. This project was undertaken to profile the provenance of the pharmacovigilance reporting of all anti-malarials, including ACT to the WHO adverse drug reaction (ADR) database (Vigibase™) over the past 40 years. Methods The WHO Programme for International Drug Monitoring, the Uppsala Monitoring Centre (UMC) provided anonymized extracts of Vigibase™ covering the period 1968-2008. All countries in the programme were clustered according to their malaria control phase and income status. The number of individual case safety reports (ICSRs) of anti-malarials was analyzed according to those clusters. Results From 1968 to 2008, 21,312 ICSRs suspecting anti-malarials were received from 64 countries. Low-income countries, that are also malaria-endemic (categorized as priority 1 countries) submitted only 1.2% of the ICSRs. Only 60 out of 21,312 ICSRs were related to ACT, 51 of which were coming from four sub-Saharan African countries. Although very few ICSRs involved artemisinin-based compounds, many of the adverse events reported were potentially serious. Conclusions This paper illustrates the low reporting of ADRs to anti-malarials in general and ACT in particular. Most reports were submitted by non-endemic and/or high-income countries. Given the current mix of large donor funding, the insufficient information on safety of these drugs, increasing availability of ACT and artemisinin-based monotherapies in public and private sector channels, associated potential for inappropriate use and finally a pipeline of more than 10 new novel anti-malarials in various stages of development, the

Background Nonmedical prescription opioid use has emerged as a major public health concern in recent years, particularly in rural Appalachia. Little is known about the routes of administration (ROA) involved in nonmedical prescription opioid use among rural and urban drug users. The purpose of this study was to describe rural-urban differences in ROA for nonmedical prescription opioid use. Methods A purposive sample of 212 prescription drug users was recruited from a rural Appalachian county (n = 101) and a major metropolitan area (n = 111) in Kentucky. Consenting participants were given an interviewer-administered questionnaire examining sociodemographics, psychiatric disorders, and self-reported nonmedical use and ROA (swallowing, snorting, injecting) for the following prescription drugs: buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, OxyContin® and other oxycodone. Results Among urban participants, swallowing was the most common ROA, contrasting sharply with substance-specific variation in ROA among rural participants. Among rural participants, snorting was the most frequent ROA for hydrocodone, methadone, OxyContin®, and oxycodone, while injection was most common for hydromorphone and morphine. In age-, gender-, and race-adjusted analyses, rural participants had significantly higher odds of snorting hydrocodone, OxyContin®, and oxycodone than urban participants. Urban participants had significantly higher odds of swallowing hydrocodone and oxycodone than did rural participants. Notably, among rural participants, 67% of hydromorphone users and 63% of morphine users had injected the drugs. Conclusions Alternative ROA are common among rural drug users. This finding has implications for rural substance abuse treatment and harm reduction, in which interventions should incorporate methods to prevent and reduce route-specific health complications of drug use. PMID:20950455

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methodology is used by performing a MEDLINE literature search to identify pertinent clinical studies on the topic and a MAUDE (U.S. Food and DrugAdministration Center for Devices and Radiological Health) database search to identify the reported complications of a given technology. Both are supplemented by accessing the "related articles" feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the Governing Board of the ASGE. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through October 2009 for articles and references related to devices and the U.S. Food and DrugAdministration by using the keywords "FDA" and "devices." In addition, the Web was searched using the same keywords. The U.S. Food and DrugAdministration website was also thoroughly reviewed. Practitioners should continue to monitor the medical literature for subsequent data about these issues. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment. PMID:20421100

The Food and DrugAdministration is a scientific regulatory agency whose consumer protection activities cover a wide range of products including foods and additives, and pesticide residues on foods; drugs; cosmetics; medical devices; and radiation-emitting electronic products. Amongst its concerns is the possible teratogen effects of regulated products to which the pregnant woman is exposed. The policies and programs of the agency directed toward reducing such risks to the unborn are reviewed. These measures include guidelines for animal reproduction studies and for clinical trials involving women to childbearing potential; labeling of products to disclose known or possible harm to the fetus or embryo; surveillance procedures designed to detect previously unsuspected adverse effects of marketed products; research activities designed to develop better understanding of developmental toxicology and improved techniques for detecting embryocidal and embryotoxic effects; and educational efforts directed both to professionals and the public regarding hazards to the unborn of agency-regulated products.

1 Mice in small groups develop a despotic type of social hierarchy, a feature of which is to resist alteration through the medium of psychotropic drugs. This makes a rapid pharmacologically induced change in the social hierarchy impossible. 2 Patrolling the territory and a certain level of social interaction are both critical factors in maintaining the phenomenon of inertia in the social hierarchy. Psychotropic drugs (diazepam, droperidol and mescaline) altered both these factors to a varying degree and also displayed a differing ability to maintain the inertia of the social hierarchy. 3 A drug-induced alteration in the level of aggression in a subordinate mouse in a group of three does not cause an alteration in its social position. 4 Chronic administration of diazepam, droperidol or mescaline, all of which alter the level of aggression in different ways, can result in an inversion of the social hierarchy where a competitive rival is present in the group of mice. The rate of inversion of the social hierarchy depends on the type of pre-existing social hierarchy. 5 It is suggested that the ability of psychotropic drugs to maintain the inertia of the hierarchy be used as an index of their effect upon certain types of species-specific behaviour; in particular aggression. PMID:7192165

The Food and DrugAdministration (FDA) is issuing a final rule to revoke a regulation requiring a cardiac pacemaker registry. The registry, which was mandated by the Deficit Reduction Act of 1984, requires any physician and any provider of services who requests or receives Medicare payment for an implantation, removal, or replacement of permanent cardiac pacemaker devices and pacemaker leads to submit certain information to the registry. The information is used by FDA to track the performance of permanent cardiac pacemakers and pacemaker leads and by the Health Care Finance Administration (HCFA) to administer its Medicare payment program for these devices. This action is being taken to implement an act to Repeal An Unnecessary Medical Device Reporting Requirement passed by Congress in 1996 to remove the cardiac pacemaker registry to eliminate duplicative and unnecessary reporting. PMID:11010690

Background Fluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. This study investigated the safety of oral administration of fluralaner at 3 times the highest expected clinical dose to Multi Drug Resistance Protein 1 (MDR1(-/-)) gene defect Collies. Methods Sixteen Collies homozygous for the MDR1 deletion mutation were included in the study. Eight Collies received fluralaner chewable tablets once at a dose of 168 mg/kg; eight sham dosed Collies served as controls. All Collies were clinically observed until 28 days following treatment. Results No adverse events were observed subsequent to fluralaner treatment of MDR1(-/-) Collies at three times the highest expected clinical dose. Conclusions Fluralaner chewable tablets are well tolerated in MDR1(-/-) Collies following oral administration. PMID:24602342

Seventeen patients with non-infectious chronic cystitis (NICC) (9 with interstitial cystitis, 6 patients with radiation cystitis, 1 with chemocystitis and 1 with lupoid cystitis) were treated with electromotive administration of intravesical lidocaine and dexamethasone followed by hydrodistension of the bladder. Complete resolution of symptoms for an average of 7.5 months was observed in 11 patients (65%), partial improvement in 4 (23.5%). In this series no complications occurred. Electromotive drugadministration (EMDA) and cystodistension were well tolerated by all patients. The treatment was performed on an outpatient basis, thus reducing therapeutic costs. The results presented demonstrate that the combination of EMDA and bladder hydrodistension is an effective first-line treatment for NICC patients. PMID:9449584

A comparison has been made between the absorption of oral medroxyprogesterone acetate (MPA) in an aqueous suspension preparation and in syrup form. Plasma drug profiles were measured after a single administration of the two formulations in 17 advanced cancer patients. On average the standard form (aqueous suspension) gave peak levels which were lower than the syrup mixture. However, the wide intersubject spread in MPA plasma levels observed in both groups did not allow any statistical significance to be assigned to this difference. PMID:2945648

Cellular therapy products are an emerging medical product class undergoing rapid scientific and clinical innovation worldwide. These products pose unique regulatory challenges both for countries with existing regulatory frameworks and for countries where regulatory frameworks for cellular therapy products are under development. The United States Food and DrugAdministration (US FDA) has a history of productive working relationships with international regulatory authorities, and seeks to extend this to the cellular therapy field. The US FDA and its global regulatory counterparts are engaged in collaborations focused on the convergence of scientific and regulatory approaches, and the education of scientists, clinicians, regulators, and the public at large on the development of cellular therapies. PMID:23021082

... Food and DrugAdministration Web site at http://www.fda.gov once finalized. (c) Agreements and... understandings will not be made available through the FDA Web site, these agreements will be available...

In a randomized crossover study on sedation in outpatient oral surgery, the relation between the serum profile and the drug effect profile for intravenously (i.v.) and rectally administered diazepam was studied. Both sedation methods were found to be equally efficient at a mean dose of 0.25 mg/kg (range, 0.14—0.45) for i.v. administration, and 0.53 mg/kg (range, 0.50—0.58) for rectal administration. Both the serum concentration and the effect reached their mean peaks at the same time; however, this was 15 min later after rectal sedation than after i.v. sedation. Intravenous administration yielded a significantly higher serum concentration of diazepam at the clinical endpoint than did rectal administration, but the mean effect levels at the clinical endpoint were equal for both sedation methods. No linear correlation between log-serum concentration and the patient's estimation of effect was found. PMID:3481512

Objective To clinically evaluate a new patented multimodal system (SAFERSleep) designed to reduce errors in the recording and administration of drugs in anaesthesia. Design Prospective randomised open label clinical trial. Setting Five designated operating theatres in a major tertiary referral hospital. Participants Eighty nine consenting anaesthetists managing 1075 cases in which there were 10 764 drugadministrations. Intervention Use of the new system (which includes customised drug trays and purpose designed drug trolley drawers to promote a well organised anaesthetic workspace and aseptic technique; pre-filled syringes for commonly used anaesthetic drugs; large legible colour coded drug labels; a barcode reader linked to a computer, speakers, and touch screen to provide automatic auditory and visual verification of selected drugs immediately before each administration; automatic compilation of an anaesthetic record; an on-screen and audible warning if an antibiotic has not been administered within 15 minutes of the start of anaesthesia; and certain procedural rules—notably, scanning the label before each drugadministration) versus conventional practice in drugadministration with a manually compiled anaesthetic record. Main outcome measures Primary: composite of errors in the recording and administration of intravenous drugs detected by direct observation and by detailed reconciliation of the contents of used drug vials against recorded administrations; and lapses in responding to an intermittent visual stimulus (vigilance latency task). Secondary: outcomes in patients; analyses of anaesthetists’ tasks and assessments of workload; evaluation of the legibility of anaesthetic records; evaluation of compliance with the procedural rules of the new system; and questionnaire based ratings of the respective systems by participants. Results The overall mean rate of drug errors per 100 administrations was 9.1 (95% confidence interval 6.9 to 11.4) with the new

The National Programme for the Elimination of Lymphatic Filariasis is underway in the endemic districts of Tamil Nadu State, South India, since 2001. Annual mass drugadministration (MDA) was carried out by the state health department to all eligible individuals. The impact of MDAs on transmission parameters was evaluated in 2 revenue blocks, viz, one with DEC alone and the other with a combination of albendazole. After 10 years with 6 annual MDAs, the transmission indices reached low levels in both treatment arms, but still persisted. However, the DEC alone arm showed higher transmission rates, compared to the DEC+ALB arm. Few villages which demonstrated persistent transmission need to be targeted with an additional control measure viz, vector control, to achieve LF elimination. It is evident from the 10 year period of the study that inclusion of albendazole along with DEC has significantly reduced the transmission indices to almost nil level, as compared to DEC alone. PMID:25205435

Objective Bladder cancer is a cause of considerable morbidity worldwide. Electromotive DrugAdministration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved. Material and Methods Electromotive DrugAdministration involves applying intravesical mitomycin C with direct current of 20 mA delivered through a catheter electrode for 30 min. For numerical electric field computation we built a 3-D nonhomogeneous patient specific model based on CT images and used finite element method simulations to determine the electric fields in the whole body. Results Results indicate that highest electric field in the bladder wall was 37.7 V/m. The mean electric field magnitude in the bladder wall was 3.03 V/m. The mean magnitude of the current density in the bladder wall was 0.61 A/m2. Conclusions The present study shows that electroporation is not the mechanism of action in EMDA. A more likely explanation of the mechanism of action is iontophoretic forces increasing the mitomycin C concentration in the bladder wall.

... Staff; Refuse To Accept Policy for 510(k)s; Availability AGENCY: Food and DrugAdministration, HHS... draft guidance entitled ``Refuse to Accept Policy for 510(k)s.'' The purpose of this document is to... (510(k)) submission is administratively complete, which determines whether it should be accepted...

Preoperative administration of pharmacological substances, such as non-steroidal anti-inflammatory drugs or opioids, has been gaining acclaim as a preemptive measure to minimize postoperative pain. This systematic review and meta-analysis aimed at evaluating the effectiveness of this approach in adults undergoing surgical procedures. MEDLINE, EMBASE and the Cochrane Central Register were searched from inception through January 2015. Data from randomized placebo-controlled trials were screened, extracted and assessed for risk of bias according to The Cochrane Collaboration's Tool by two independent authors. The primary outcome measure was reduction in postoperative analgesic consumption during 24 h post surgery; effects were described as mean differences between the drug and placebo arms with corresponding 95% confidence intervals (CIs) and were pooled using random-effects models. Potential publication bias was tested using funnel plots and Egger's regression test for funnel plot asymmetry. Screened were 511 records, of which 39 were included in the final synthesis with data from 3172 patients. A significant reduction in postoperative analgesic consumption was observed using preoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs; 95% CI, -0.61 to -0.14; 31 comparisons), chiefly by the COX-2 inhibitors class (95% CI, -0.95 to -0.33; 13 comparisons). Significant reduction was also observed for gabapentin (95% CI, -1.60 to -0.38; 6 comparisons). No significant effects were observed using opioids, propionic acids or oxicam derivatives. WHAT DOES THIS REVIEW ADD?: Current analyses endorse the effectiveness of COX-2 inhibitors and gabapentin in reducing acute postoperative pain when administered preemptively presurgery. Such corroboration is not found for opioids and other NSAID classes. PMID:26991963

Social-learning theories of substance use propose that members of peer groups influence the drug use of other members by selectively modeling, reinforcing, and punishing either abstinence-related or drug-related behaviors. The objective of the present study was to examine social influences on cocaine self-administration in isolated and socially housed rats, with the caveat that the socially housed rats were tested simultaneously with their partner in the same chamber. To this end, male rats were obtained at weaning and housed in isolated or pair-housed conditions for 6 weeks. Rats were then implanted with intravenous catheters and cocaine self-administration was examined in custom-built operant conditioning chambers that allowed two rats to be tested simultaneously. For some socially housed subjects, both rats had simultaneous access to cocaine; for others, only one rat of the pair had access to cocaine. An econometric analysis was applied to the data, and the reinforcing strength of cocaine was measured by examining consumption (i.e., quantity demanded) and elasticity of demand as a function of price, which was manipulated by varying the dose and ratio requirements on a fixed ratio schedule of reinforcement. Cocaine consumption decreased as a function of price in all groups. Elasticity of demand did not vary across groups, but consumption was significantly lower in socially housed rats paired with a rat without access to cocaine. These data suggest that the presence of an abstaining peer decreases the reinforcing strength of cocaine, thus supporting the development of social interventions in drug abuse prevention and treatment programs. PMID:23412112

Social-learning theories of substance use propose that members of peer groups influence the drug use of other members by selectively modeling, reinforcing, and punishing either abstinence-related or drug-related behaviors. The objective of the present study was to examine the social influences on cocaine self-administration in isolated and socially housed rats, under conditions where the socially housed rats were tested simultaneously with their partner in the same chamber. To this end, male rats were obtained at weaning and housed in isolated or pair-housed conditions for 6 weeks. Rats were then implanted with intravenous catheters and cocaine self-administration was examined in custom-built operant conditioning chambers that allowed two rats to be tested simultaneously. For some socially housed subjects, both rats had simultaneous access to cocaine; for others, only one rat of the pair had access to cocaine. An econometric analysis was applied to the data, and the reinforcing strength of cocaine was measured by examining consumption (i.e. quantity demanded) and elasticity of demand as a function of price, which was manipulated by varying the dose and ratio requirements on a fixed ratio schedule of reinforcement. Cocaine consumption decreased as a function of price in all groups. Elasticity of demand did not vary across groups, but consumption was significantly lower in socially housed rats paired with a rat without access to cocaine. These data suggest that the presence of an abstaining peer decreases the reinforcing strength of cocaine, thus supporting the development of social interventions in drug abuse prevention and treatment programs. PMID:23412112

Background The World Health Organization (WHO) Global Program to Eliminate Lymphatic Filariasis relies on mass drugadministration (MDA) of two drugs annually for 4 to 6 years. The goal is to reduce the reservoir of microfilariae in the blood to a level insufficient to maintain transmission by the mosquito vector. In 2008, the international medical aid organization Médecins Sans Frontières (MSF) performed the first round of a MDA in the high-burden area of Asmat district, in Papua, Indonesia. We report the challenges faced in this MDA on a remote Indonesian island and propose solutions to overcome these hurdles in similar future contexts. Results During the MDA, we encountered difficult challenges in accessing as well as persuading the patient population to take the antifilarial drugs. Health promotion activities supporting treatment need to be adapted and repetitive, with adequate time and resources allocated for accessing and communicating with local, seminomadic populations. Distribution of bednets resulted in an increase in MDA coverage, but it was still below the 80-85% target. Conclusions MDA for lymphatic filariasis is how the WHO has planned to eliminate the disease from endemic areas. Our programmatic experience will hopefully help inform future campaign planning in difficult-to-access, high-burden areas of the world to achieve target MDA coverage for elimination of lymphatic filariasis. PMID:20701744

The Mass DrugAdministration (MDA) done in Surat city (Gujarat) during 2005, revealed good impact on infection and infectivity in mosquitoes and also on microfilaria rate & mean infection density. The overall impact seen was 23% on mf rate, 28% on mean mf density, 65% on infection rate and 50% on infectivity rate in vectors. Indigenous population contribution to microfilaria cases was 9.7%, whereas migratory population contributed 72.2%; predominant 51.9% from Orissa and 20.3% from U.P. Of the total 3640 persons interviewed for MDA compliance in seven zones of the Surat city revealed that actual drug consumption was 76.7% (2792/3640). Another 11.9% although took the drug but did not consume and 11.4% refused. Important reasons for consuming was fear to get the disease (40.7%) and for not consuming; 'will consume after meal' (6.9%), too many tablets (1.7%), seek consent from doctor (1.5%), lack of awareness (1.4%) etc. Refusal was mainly due to the reason as respondents felt apparently healthy. Assessment of IEC activities suggested that main awareness was created by media (local or national TV, banners or handbills, local news papers or mike announcement) alongwith some impact made through NGO's. These observations clearly indicated the utility of effective health education for optimum community participation and shown that it was crucial for successful community based elimination campaign. However some gray areas also suggest the scope for further improvements. PMID:17370677

The Food and DrugAdministration (FDA) is classifying the nonimplanted, peripheral electrical continence device into class II (special controls). The special controls that will apply to this device are set forth below. The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, and the Food and DrugAdministration Modernization Act of 1997. The agency is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. PMID:11010624

Purpose The increase in online purchasing of medications raises safety concerns regarding teratogenic drugs. The use of the teratogenic drug ‘isotretinoin’ for women of childbearing age requires strict adherence to the Pregnancy Prevention Programme (PPP), a risk minimisation measure imposed on prescribers and users. We sought to determine how readily consumers can purchase isotretinoin online and the associated safety procedures and information. Methods A descriptive cross-sectional survey was conducted of 50 e-pharmacies identified from commonly used search engines. E-pharmacy characteristics and isotretinoin PPP specific criteria were evaluated. Purchases of isotretinoin from seven e-pharmacies not bearing authentication logos and not requiring a prescription were assessed for PPP policy adherence, purchasing procedures and compound quality. Results Forty-three (86%) of the e-pharmacies did not have an authentication seal/logo. Isotretinoin could be purchased from 42 sites without a valid prescription. Information on isotretinoin causing birth defects was lacking in 25 of the 50 sites, on not taking isotretinoin in pregnancy in 24 sites and not taking isotretinoin if planning or at risk of a pregnancy in 33 sites. Of the eight attempted purchases, seven arrived, all without any patient information leaflet. All were verified as isotretinoin. Conclusion The Internet provides a loophole for purchasing of medications known to cause congenital abnormalities, which needs to be addressed by medicines regulatory agencies worldwide. The current PPP for isotretinoin may be failing to protect mothers and babies from preventable harm—clinicians need to be aware of this, and the public needs to be educated about the potential risks. PMID:24493556

The ethical challenges of reporting and managing adverse events (AEs) and serious AEs (SAEs) in the context of mass drugadministration (MDA) for the treatment of neglected tropical diseases (NTDs) require reassessment of domestic and international policies on a global scale. Although the World Health Organization has set forth AE/SAE guidelines specifically for NTD MDA that incorporate suspected causality, and recommends that only SAEs get reported in this setting, most regulatory agencies continue to require the reporting of all SAEs exhibiting even a merely temporal relationship to activities associated with an MDA program. This greatly increases the potential for excess "noise" and undue risk aversion and is not only impractical but arguably unethical where huge proportions of populations are being treated for devastating diseases, and no good baseline exists against which to compare possible AE/SAE reports. Other population-specific variables that might change the way drug safety ought to be assessed include differing efficacy rates of a drug, background morbidity/mortality rates of the target disease in question, the growth rate of the incidence of disease, the availability of rescue or salvage therapies, and the willingness of local populations to take risks that other populations might not. The fact that NTDs are controllable and potentially eradicable with well-tolerated, effective, existing drugs might further alter our assessment of MDA safety and AE/SAE tolerability. At the same time, diffuseness of population, communication barriers, lack of resources, and other difficult surveillance challenges may present in NTD-affected settings. These limitations could impair the ability to monitor an MDA program's success, as well as hinder efforts to obtain informed consent or provide rescue therapy. Denying beneficial research interventions and MDA programs intended to benefit millions requires sound ethical justification based on more than the identification of

An innovative nanocapsule formulation for parenteral administration using selected vegetable oils (mango, jojoba, pequi, oat, annatto, calendula, and chamomile) was developed that has the potential to encapsulate various drugs. The vegetable oil-loaded nanocapsules were prepared by interfacial deposition and compared with capric/caprylic triglyceride-loaded lipid core nanocapsules. The major objective was to investigate the effect of vegetable oils on particle size distribution and physical stability and to determine the hemolytic potential of the nanocapsules, considering their applicability for intravenous administration. Taking into account the importance of accurately determining particle size for the selected route of administration, different size characterization techniques were employed, such as Laser Diffraction, Dynamic Light Scattering, Multiple Light Scattering, Nanoparticle Tracking Analysis, and Transmission Electronic Microscopy. Laser diffraction studies indicated that the mean particle size of all nanocapsules was below 300 nm. For smaller particles, the laser diffraction and multiple light scattering data were in agreement (D[3,2]-130 nm). Dynamic light scattering and nanoparticle tracking analysis, two powerful techniques that complement each other, exhibited size values between 180 and 259 nm for all nanoparticles. Stability studies demonstrated a tendency of particle creaming for jojoba-nanocapsules and sedimentation for the other nanoparticles; however, no size variation occurred over 30 days. The hemolysis test proved the hemocompatibility of all nanosystems, irrespective of the type of oil. Although all developed nanocapsules presented the potential for parenteral administration, jojoba oil-loaded nanocapsules were selected as the most promising nanoformulation due to their low average size and high particle size homogeneity. PMID:27433581

Introduction Implementation of Mass DrugAdministration (MDA) in urban settings is an obstacle to Lymphatic Filariasis (LF) elimination. No urban-specific guidelines on MDA in urban areas exist. Malindi district urban area had received 4 MDA rounds by the time the current study was implemented. Programme data showed average treatment coverage of 28.4% (2011 MDA), far below recommended minimum of 65–80%. Methods To identify, design and test strategies for increased treatment coverage in urban areas, a quasi-experimental study was conducted in Malindi urban area. Three sub-locations with lowest treatment coverage in 2011 MDA were purposively selected. In the pre-test phase, 947 household heads sampled using systematic random method were interviewed for quantitative data. For qualitative data, 12 Focus Group Discussions (FGDs) with single sex adult and youth male and female groups and 3 with community drug distributors (CDDs) were conducted. Forty in-depth interviews with opinion leaders and self-administered questionnaires with District Public Health officers purposively selected were carried out. The quantitative data were analyzed using SPSS version 16 and statistical significance assessed by χ2 test.The qualitative data were analyzed manually according to study's themes. Results and Discussion The identified strategies were implemented prior to and during 2012 MDA in two sub-locations (experimental) while in the third (control), usual MDA strategies were applied. In the post-test phase, 2012 MDA coverage in experimental and control sub-locations was comparatively assessed for effect of the newly designed strategies on urban MDA. Results indicated improved treatment coverage in experimental sub-locations, 77.1% in Shella and 66.0% in Barani. Central (control) sub-location also attained high coverage, 70.4% indicating average treatment coverage of 71%. Conclusion The identified strategies contributed to increased treatment coverage in experimental sites and

Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of stopping transmission of lymphatic filariasis (LF) through yearly mass drugadministration (MDA). Although preliminary surveys of the human population in Mali suggested that Wuchereria bancrofti infection was highly endemic in the Sikasso district, baseline entomological data were required to confirm high levels of transmission prior to the selection of villages in this region for a study of the impact of MDA on transmission of LF by anopheline vectors. Methods W. bancrofti transmission was assessed in 2001 (pre-MDA) and 2002 (post-MDA) in the Central District of Sikasso in southern Mali by dissection of Anopheles mosquitoes caught using the human landing catch (HLC) method. The relative frequencies and molecular forms of An. gambiae complex were determined. Results The majority (86%) of the anopheline vectors captured were identified as An. gambiae complex, and these accounted for >90% of the entomological inoculation rate (EIR) during both years of the study. There was a dramatic decrease in the number of An. gambiae complex mosquitoes captured and in the An. gambiae complex infectivity rates following MDA, accounting for the observed decrease in EIR in 2002 (from 12.55 to 3.79 infective bites per person during the transmission season). An. funestus complex mosquitoes were responsible for a low level of transmission, which was similar during both years of the study (1.2 infective bites per person during the transmission season in 2001 and 1.03 in 2002). Conclusions Based on the entomological data from this study, the district of Sikasso was confirmed as an area of high W. bancrofti transmission. This led to the selection of this area for a multi-national study on the effects of MDA on LF transmission by anopheline vectors. Comparison of vector transmission parameters prior to and immediately following the first round of MDA demonstrated a significant

The debate surrounding access to RU-486 in the US resurfaced in July 1992 when a pregnant California Resident attempted to challenge the Food and DrugAdministration (FDA) import ban by going through customs at Kennedy International Airport with 12 prescription RU-486 pills she obtained in England. The pills were confiscated and the US Supreme Court denied the woman's request to recover the pills by a 7-2 vote. In 1993, on the 20th anniversary of the Roe v Wade abortion decision, President Clinton instructed the FDA to assess the real health and safety risks of the drug and rescind the ban if politics turns out to be the central issue. FDA has no criteria for measuring acceptable levels of safety, and drug approval is a lengthy process. Moreover, clinical trials are not initiated until a pharmaceutical company applies for FDA approval, which Roussel-Uclaf, RU-486's developer, has not done despite a wealth of safety and effectiveness data amassed in Europe. In fact, fearing a consumer boycott of its other products by US anti-abortion groups, Roussel-Uclaf has limited American researchers' access to RU-486. Despite the pro-choice climate of the Clinton Administration, it is unlikely that RU-486 will be available any time soon to US women, and physicians are concerned that a black market for the drug will emerge. This likelihood has serious consequences for people with Cushing's disease, nonmalignant brain tumors, breast cancer, and other medical conditions that may be responsive to RU-486. Given the experience with the introduction of oral contraceptives, marketed before long-term health consequences had been sufficiently explored, it is essential that FDA researchers investigate the impact of RU-486 on future children, future fertility, its interaction with other medications and contraceptives, and its effects on other bodily systems. At the same time, any risk-benefit assessment must be based on scientific merit, and access to Ru-486 cannot be denied on political

The objective of this study is to clarify the influence of fluid volume in the gastrointestinal (GI) tract on the oral drug absorption. In vivo rat luminal concentrations of FITC-dextran (FD-4), a nonabsorbable marker, and drugs (metoprolol and atenolol) after oral coadministration as solutions with different osmolarity were determined by direct sampling of residual water in each segment of the GI tract. The luminal FD-4 concentration after oral administration as hyposmotic solution was significantly higher than that after administration as isosmotic or hyperosmotic solution. As the change in FD-4 concentration reflects the change in the volume of luminal fluid, it indicated that the luminal volume was greatly influenced by osmolality of solution ingested orally. Then, fraction of drug absorbed (Fa) in these segments was calculated by comparing the area under the luminal concentration-time curve of FD-4 with those of drugs. Fa values of two model drugs in each GI segment decreased with increase in luminal fluid volume, and the impact of the fluid volume was marked for Fa of atenolol (a low permeable drug) than for that of metoprolol (a high permeable drug). These findings should be beneficial to assure the effectiveness and safety of oral drug therapy. PMID:25821198

Recommendations on accidental radioactive contamination of human food were issued in 1982 by the Food and DrugAdministration (FDA). The recommendations provided guidance to State and local government officials in the exercise of their respective authorities, and were applicable to emergency response planning and to the conduct of radiation protection activities associated with the production, processing, distribution, and use of human food accidentally contaminated with radioactive material. Review of the 1982 FDA recommendations, stimulated by the events following the 1986 accident at Chernobyl, indicated that it would be appropriate to update the recommendations to incorporate newer scientific information and radiation protection philosophy, to include experience gained since 1982, and to take into account international advances. This paper presents a brief outline of the FDA`s approach to its draft revision. the most recent draft was circulated for interagency review in November 1994. Modification made in response to the comments received are included in this paper. 20 refs., 6 tabs.

As a part of ongoing efforts of the NCI-FDA Interagency Oncology Task Force subcommittee on molecular diagnostics, members of the Clinical Proteomic Technology Assessment for Cancer program of the National Cancer Institute have submitted 2 protein-based multiplex assay descriptions to the Office of In Vitro Diagnostic Device Evaluation and Safety, US Food and DrugAdministration. The objective was to evaluate the analytical measurement criteria and studies needed to validate protein-based multiplex assays. Each submission described a different protein-based platform: a multiplex immunoaffinity mass spectrometry platform for protein quantification, and an immunological array platform quantifying glycoprotein isoforms. Submissions provided a mutually beneficial way for members of the proteomics and regulatory communities to identify the analytical issues that the field should address when developing protein-based multiplex clinical assays. PMID:20007858

Methyl mercury was determined by the US Food and DrugAdministration (FDA) in 220 samples of canned tuna collected in 1991. Samples were chosen to represent different styles, colors, and packs as available. Emphasis was placed on water-packed tuna, small can size, and the highest-volume brand names. The average methyl mercury (expressed as Hg) found for the 220 samples was 0.17 ppm; the range was <0.10-0.75 ppm. Statistically, a significantly higher level of methyl mercury was found in solid white and chunk tuna. Methyl mercury level was not related to can size. None of the 220 samples had methyl mercury levels that exceeded the 1 ppm FDA action level. 11 refs., 1 tab.

Bhaishajya Kaala (time of drugadministration) is an important principle to be considered while treating a disease. Still hardly a handful of physicians are seen, who account for this. To highlight its imperial role in Chikitsa, there is an immense necessity to analyze this concept, which is the need of the hour. Bhaishajya Kaala is mainly explained in relation with Bala of Roga, Rogi, particular Dosha, Dooshya, and various other factors. The comprehensive understanding of this concept involves so many questions as, why there is a difference in the number of Aushdha Kaala? What is the logic behind their indications as well as contraindications? The present paper focuses on the above points to find out the convincing answers. PMID:24049398

Although many people welcome the recent move by the United States to give its Food and DrugAdministration (fda) the authority to regulate the content of tobacco, some worry that such regulation constitutes unwarranted interference with the freedom of competent adult tobacco consumers. The concern for protecting the autonomy of individuals is valuable indeed, but given the highly addictive nature of tobacco products (and especially the nicotine in tobacco products), the continued use of tobacco by smokers cannot —without straining credulity—be said to be autonomous. This fact, combined with a proper construal of the fda’s role and an appreciation of the substantial morbidity and mortality associated with tobacco use, makes a strong case for content regulation. PMID:20697516

The Food and DrugAdministration (FDA) introduced changes in labeling and indications for use to testosterone products in 2015 due to a possible increased risk of cardiovascular (CV) events. This decision was made based on six clinical studies—some that supported an increased CV risk, and some that did not. Since this decision, additional studies have been published examining the interplay between hypogonadism, CV risk, and testosterone, demonstrating that the risk may be lower than originally estimated. Clinicians are placed in a difficult position, as studies support an increased mortality risk in hypogonadal men, but also an increased risk of CV events in men on testosterone therapy. As a result, many clinicians will be more selective in their prescribing of testosterone. In this review, we examine how these new guidelines arose and how they may affect prescribing habits. PMID:27141448

Based on the action plan "Ensuring a stable supply of National Immunization Program vaccines and sovereignty of biopharmaceutical products," Korea Food and DrugAdministration (KFDA) has made efforts to develop vaccines in the context of self reliance and to protect public health. Along with the recognized infrastructures for clinical trials, clinical trials for vaccines have also gradually been conducted at multinational sites as well as at local sites. KFDA will support to expand six to eleven kinds of vaccines by 2017. In accordance with integrated regulatory system, KFDA has promoted clinical trials, established national lot release procedure, and strengthened good manufacturing practices inspection and post marketing surveillance. Against this backdrop, KFDA will support the vaccine development and promote excellent public health protection. PMID:23596594

Prior to 1989 {sup 99}Mo was produced in the US by a single supplier, Cintichem Inc., Tuxedo, NY. Because of problems associated with operating its facility, in 1989 Cintichem elected to decommission the facility rather than incur the costs for repair. The demise of the {sup 99}Mo capability at Cintichem left the US totally reliant upon a single foreign source, Nordion International, located in Ottawa Canada. In 1992 the DOE purchased the Cintichem {sup 99}Mo Production Process and Drug Master File (DMF). In 1994 the DOE funded Sandia National Laboratories (SNL) to produce {sup 99}Mo. Although Cintichem produced {sup 99}Mo and {sup 99m}Tc generators for many years, there was no requirement for process validation which is now required by the Food and DrugAdministration (FDA). In addition to the validation requirement, the requirements for current Good manufacturing Practices were codified into law. The purpose of this paper is to describe the process validation being conducted at SNL for the qualification of SNL as a supplier of {sup 99}Mo to US pharmaceutical companies.

Mass drugadministration (MDA) was a component of many malaria programs during the eradication era, but later was seldomly deployed due to concerns regarding efficacy and feasibility and fear of accelerating drug resistance. Recently, however, there has been renewed interest in the role of MDA as an elimination tool. Following a 2013 Cochrane Review that focused on the quantitative effects of malaria MDA, we have conducted a systematic, qualitative review of published, unpublished, and gray literature documenting past MDA experiences. We have also consulted with field experts, using their historical experience to provide an informed, contextual perspective on the role of MDA in malaria elimination. Substantial knowledge gaps remain and more research is necessary, particularly on optimal target population size, methods to improve coverage, and primaquine safety. Despite these gaps, MDA has been used successfully to control and eliminate Plasmodium falciparum and P. vivax malaria in the past, and should be considered as part of a comprehensive malaria elimination strategy in specific settings. PMID:26013371

Stimulants, together with anabolic androgenic steroids, are regarded as one of the most popular doping substances in sport. Owing to a great variety of these substances and new designer drugs being introduced to the market, each year the World Anti-Doping Agency (WADA) updates the list of substances and methods prohibited in sport. On 1 January 2014, a new doping agent - trimetazidine (TMZ) - was added to the WADA Prohibited List. TMZ, a substance prohibited in competition, is classified in the S6b Specified Stimulant Group. TMZ is used as a well-known cardiologic drug with confirmed biochemical and clinical activity. According to knowledge of the pharmacology and mechanism of TMZ action, TMZ can be used by athletes to improve physical efficiency, especially in the case of endurance sports. This study presents the phenomena of TMZ use by Polish athletes involved in anti-doping control in the WADA-accredited laboratory in Warsaw (Poland) between 2008 and 2013. Samples were taken from the athletes of such disciplines as cycling, athletics, and triathlon. Moreover, the elimination study of TMZ has been conducted to establish the change of TMZ concentration in urine sample after oral administration of a single or double (during the long-term therapy) dose. TMZ was monitored in urine samples by gas chromatography-mass spectrometry-nitrogen phosphorus detection (GC-MS-NPD). PMID:25421604

Background Blinding trachoma, caused by the bacteria Chlamydia trachomatis, is a neglected tropical disease targeted for elimination by 2020. A major component of the elimination strategy is mass drugadministration (MDA) with azithromycin. Currently, program decisions are made based on clinical signs of ocular infection, but we have been investigating the use of antibody responses for post-MDA surveillance. In a previous study, IgG responses were detected in children lacking clinical evidence of trachoma, suggesting that IgG responses represented historical infection. To explore the utility of serology for program evaluation, we compared IgG and IgA responses to trachoma antigens and examined changes in IgG and IgA post-drug treatment. Methods Dried blood spots and ocular swabs were collected with parental consent from 264 1–6 year olds in a single village of Kongwa District, central Tanzania. Each child also received an ocular exam for detection of clinical signs of trachoma. MDA was given, and six months later an additional blood spot was taken from these same children. Ocular swabs were analyzed for C. trachomatis DNA and antibody responses for IgA and total IgG were measured in dried bloods spots. Results Baseline antibody responses showed an increase in antibody levels with age. By age 6, the percentage positive for IgG (96.0%) was much higher than for IgA (74.2%). Antibody responses to trachoma antigens declined significantly six months after drug treatment for most age groups. The percentage decrease in IgA response was much greater than for IgG. However, no instances of seroreversion were observed. Conclusions Data presented here suggest that focusing on concordant antibody responses in children will provide the best serological surveillance strategy for evaluation of trachoma control programs. PMID:24755001

Drug-induced akinesia is a potential cause of pressure ulcers. However, pressure ulcers that are caused by drug-induced akinesia are not considered an adverse drug reaction (ADR). We propose that drug-induced pressure ulcers (DIPU) are pressure ulcers that are caused by an external force that is experienced after drugadministration, and we considered resolution of these ulcers after drug discontinuation to be a supportive finding. In this report, we reviewed the medical records of pressure ulcer cases from a 300-bed hospital. Among 148 patients, four patients with pressure ulcers met the criterion for DIPU. In these cases, the suspected DIPU were related to treatment with olanzapine, fluvoxamine, valproic acid, clotiazepam, triazolam and rilmazafone. These drugs were administrated to manage the patients' behavioral and psychological symptoms that accompanied dementia. The DIPU in these patients were categorized as stage IV according to the National Pressure Ulcer Advisory Panel criteria. Discontinuation of the causal drugs led to significant improvements or complete healing of the pressure ulcers, and the patients subsequently recovered their mobility. Therefore, we propose that DIPU are potential ADR that have been overlooked in clinical practice. Thus, recognition of DIPU as an ADR may be important in preventing and appropriately managing pressure ulcers among elderly patients. PMID:26364579

Clinically, central nervous system (CNS) disorders account for more hospitalisations and prolonged care than almost all other diseases combined. In the preclinical setting, the intracerebroventricular (ICV) route for cerebrospinal fluid (CSF) sampling or dose administration in rodent models of human CNS disorders has potential to provide key insight on the pathobiology of these conditions. Low level neuroinflammation is present in >40% of patients with severe depression or schizophrenia and so comparative assessment of CSF composition between patients and rodent models of CNS disorders is potentially invaluable for hypothesis generation and for assessing rodent model validity. As molecules in the CSF have relatively low protein binding and are freely exchanged into the extracellular fluid of the brain parenchyma, supraspinal drugadministration into the CSF can produce therapeutic drug concentrations in the brain. Direct administration of investigational agents into the CSF of the lateral ventricle of the brain enables intrinsic efficacy and adverse effect profiles to be evaluated without the confounding effects of drug metabolism, due to the low capacity of the CNS to metabolise exogenous compounds. It is our view that the ICV route for CSF sampling and for administration of novel drugs in development is under-utilised in preclinical research on CNS disorders. This is due to the high degree of technical skill and low margin for error associated with correct ICV guide cannula implantation in the rat. However, these technical challenges can be overcome by using standardised procedures and attention to detail during surgery and in the post-operative period. PMID:24937765

The concept of a technological quick fix or 'magic-bullet' for control and elimination of Neglected Tropical Diseases (NTDs) is flawed. NTDs are embedded within complex biological and social systems that are shaped by ecological and political contexts. This commentary emphasises the need for implementation research to address implementation gaps in the control of NTDs. With a specific focus on sub-Saharan Africa and helminth diseases amenable to preventive chemotherapy through mass drugadministration, we explore the important role of context, programme partnerships and community in achieving equitable and effective NTD control. PMID:27481833

Background Less is known about mass drugadministration [MDA] for neglected tropical diseases [NTDs] than is suggested by those so vigorously promoting expansion of the approach. This paper fills an important gap: it draws upon local level research to examine the roll out of treatment for two NTDs, schistosomiasis and soil-transmitted helminths, in Uganda. Methods Ethnographic research was undertaken over a period of four years between 2005-2009 in north-west and south-east Uganda. In addition to participant observation, survey data recording self-reported take-up of drugs for schistosomiasis, soil-transmitted helminths and, where relevant, lymphatic filariasis and onchocerciasis was collected from a random sample of at least 10% of households at study locations. Data recording the take-up of drugs in Ministry of Health registers for NTDs were analysed in the light of these ethnographic and social survey data. Results The comparative analysis of the take-up of drugs among adults revealed that although most long term residents have been offered treatment at least once since 2004, the actual take up of drugs for schistosomiasis and soil-transmitted helminths varies considerably from one district to another and often also within districts. The specific reasons why MDA succeeds in some locations and falters in others relates to local dynamics. Issues such as population movement across borders, changing food supply, relations between drug distributors and targeted groups, rumours and conspiracy theories about the 'real' purpose of treatment, subjective experiences of side effects from treatment, alternative understandings of affliction, responses to social control measures and historical experiences of public health control measures, can all make a huge difference. The paper highlights the need to adapt MDA to local circumstances. It also points to specific generalisable issues, notably with respect to health education, drug distribution and more effective use of

Purpose To describe the fabrication, evaluation, and preliminary in vivo safety of a new drug delivery system (DDS) for topical anti–TNF-α antibody administration. Methods A DDS was fabricated using inverse template fabrication of a hydrophobic three-dimensional porous scaffold (100–300 μm in diameter porosity) loaded with 10% polyvinyl alcohol hydrogel carrying 5 mg/ml (weight/volume) of anti–TNF-α antibody. Drug-loaded DDS was sterilized with 25 kGy of gamma irradiation. Long-term in vitro antibody affinity and release was evaluated at room temperature or 37°C using enzyme-linked immunosorbent assay (ELISA) and protein fluorescence. In vivo clinical and histolopathological assessment was performed by subcutaneous implantation in BALB/c mice for 3 months. Results Gamma irradiation, repeated dry/wet cycles, and storage at room temperature for 1 year or 37°C for 1 month had no deleterious effects on antibody affinity. Anti–TNF-α release was high during the first minutes of aqueous exposure, followed by stabilization and gradual, low-dose, antibody release over the next 30 days. Histopathologic evaluation of explanted DDS showed a fibrous pseudocapsule and a myxoid acute/chronic inflammation without granuloma formation surrounding the implants. Conclusions Sustained local delivery of anti–TNF-α antibody is feasible using the described DDS, which provides stability of the enclosed antibody for up to 1 year of storage. Preliminary results show good in vivo tolerance following subcutaneous placement for 3 months. The proposed fabrication and sterilization process opens new possibilities for the delivery of biologic agents to the anterior surface of the eye. Translational Relevance The described DDS will facilitate the treatment of ocular surface diseases amenable to biologic therapy. PMID:26981333

Background Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drugadministration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can be stopped within an LF evaluation unit (EU) after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings. Methodology The TAS was conducted twice in each EU with TAS-1 and TAS-2 approximately 24 months apart. Lot quality assurance sampling (LQAS) formed the basis of the TAS survey design but specific EU characteristics defined the survey site (school or community), eligible population (6–7 year olds or 1st–2nd graders), survey type (systematic or cluster-sampling), target sample size, and critical cutoff (a statistically powered threshold below which transmission is expected to be no longer sustainable). The primary diagnostic tools were the immunochromatographic (ICT) test for W. bancrofti EUs and the BmR1 test (Brugia Rapid or PanLF) for Brugia spp. EUs. Principal Findings/Conclusions In 10 of 11 EUs, the number of TAS-1 positive cases was below the critical cutoff, indicating that MDA could be stopped. The same results were found in the follow-up TAS-2, therefore, confirming the previous decision outcome. Sample sizes were highly sex and age-representative and closely matched the target value after factoring in estimates of non-participation. The TAS was determined to be a practical and effective evaluation tool for stopping MDA although its validity for longer-term post-MDA surveillance

Antibiotic resistance (ABR) is a global public health threat. Despite the emergence of highly resistant organisms and the huge medical need for new drugs, the development of antibacterials has slowed to an unacceptable level worldwide. Numerous government and non-government agencies have called for public-private partnerships and innovative funding mechanisms to address this problem. To respond to this public health crisis, the Innovative Medicines Initiative Joint Undertaking programme has invested more than €660 million, with a goal of matched contributions from the European Commission and the European Federation of Pharmaceutical Industries and Associations, in the development of new antibacterial strategies. The New Drugs for Bad Bugs (ND4BB) programme, an Innovative Medicines Initiative, has the ultimate goal to boost the fight against ABR at every level from basic science and drug discovery, through clinical development to new business models and responsible use of antibiotics. Seven projects have been launched within the ND4BB programme to achieve this goal. Four of them will include clinical trials of new anti-infective compounds, as well as epidemiological studies on an unprecedented scale, which will increase our knowledge of ABR and specific pathogens, and improve the designs of the clinical trials with new investigational drugs. The need for rapid concerted action has driven the funding of seven topics, each of which should add significantly to progress in the fight against ABR. ND4BB unites expertise and provides a platform where the commitment and resources required by all parties are streamlined into a joint public-private partnership initiative of unprecedented scale. PMID:26568581

Background Lymphatic filariasis (LF) is targeted for elimination through annual mass drugadministration (MDA) for 4–6 years. In 2006, Zanzibar stopped MDA against LF after five rounds of MDA revealed no microfilaraemic individuals during surveys at selected sentinel sites. We asked the question if LF transmission was truly interrupted in 2006 when MDA was stopped. Methodology/Principal Findings In line with ongoing efforts to shrink the LF map, we performed the WHO recommended transmission assessment surveys (TAS) in January 2012 to verify the absence of LF transmission on the main Zanzibar islands of Unguja and Pemba. Altogether, 3275 children were tested on both islands and 89 were found to be CFA positive; 70 in Pemba and 19 in Unguja. The distribution of schools with positive children was heterogeneous with pronounced spatial variation on both islands. Based on the calculated TAS cut-offs of 18 and 20 CFA positive children for Pemba and Unguja respectively, we demonstrated that transmission was still ongoing in Pemba where the cut-off was exceeded. Conclusions Our findings indicated ongoing transmission of LF on Pemba in 2012. Moreover, we presented evidence from previous studies that LF transmission was also active on Unguja shortly after stopping MDA in 2006. Based on these observations the government of Zanzibar decided to resume MDA against LF on both islands in 2013. PMID:25816287

Despite the growing market for obesity care, the US Food and DrugAdministration (FDA) has approved only two new pharmaceutical agents-lorcaserin and combination phentermine/topiramate-for weight reduction since 2000, while removing three agents from the market in the same time period. This article explores the FDA's history and role in the approval of anti-obesity medications within the context of a public health model of obesity. Through the review of obesity literature and FDA approval documents, we identified two major barriers preventing fair evaluation of anti-obesity agents including: (1) methodological pitfalls in clinical trials and (2) misaligned values in the assessment of anti-obesity agents. Specific recommendations include the use of adaptive (Bayesian) design protocols, value-based analyses of risks and benefits, and regulatory guidance based on a comprehensive, multi-platform obesity disease model. Positively addressing barriers in the FDA approval process of anti-obesity agents may have many beneficial effects within an obesity disease model. PMID:26626768

To assess retailer compliance with Food and DrugAdministration (FDA) regulations on tobacco sales and advertising practices, including point-of-sale advertisements, in two distinct Columbus, Ohio neighborhood groups by income. Data were gathered from a random sample of 129 licensed tobacco retailers, which included data on both exterior and interior advertisements as well as sales practices. Descriptive analyses compared retail outlets by high and low income neighborhood locations. Compliance with FDA regulations was high in the random sample of urban tobacco retail outlets. None of the retail outlets sold loose cigarettes or offered free items with purchase. Less than 10% of the outlets surveyed offered self-service access to cigarettes or smokeless tobacco products. From all surveyed retail outlets 95% had cigarette, 57% had smokeless, and 57% had cigar advertisements at the point-of-sale. There were no significant differences in compliance by income, but the mean number of advertisements on the building and self-service access to cigars was significantly different by neighborhood income. There was a high degree of compliance with the new FDA regulation on tobacco marketing and sales practices in urban retail tobacco outlets in Columbus, Ohio. Tobacco advertising and marketing remain highly prevalent in retail outlets, with some significant differences between high and low income neighborhoods. PMID:22197961

mHealth smartphone applications (apps) offer great promise for managing people with diabetes, as well as those with prediabetes. But to realize that potential, industry needs to get clarity from the U.S. Food and DrugAdministration (FDA) regarding the scope of its regulatory oversight. Certain smartphone apps, when properly understood, simply help people live healthier lives, assisting with dietary choices, monitoring exercise, and recording other factors important to overall health. The manufacturers of such apps, in an effort to promote their products but also to educate customers, might wish to explain how using the app can help reduce the risk of developing diabetes. Right now, though, the mere mention of the disease "diabetes" would cause the app to be regulated by the FDA. Such regulation, we submit, discourages the kind of education and motivational messages that our country needs to stem the tide of this disease. Further, should the app simply receive data from a blood glucose meter and graph that data for easier comprehension by the patient, the app would become a class II medical device that requires FDA clearance. Again, we submit that such simple software functionality should not be so discouraged. In this article, we identify the issues that we believe need to be clarified by the FDA in order to unleash the potential of mHealth technology in the diabetes space. PMID:23566984

A network of computers is being used to support the Food and DrugAdministration's Bureau of Foods mass spectrometry facility. Five mass spectrometers are each interfaced to at least 2 of the 6 dedicated minicomputers in the laboratory. This multiple interfacing provides data acquisition and processing backup, reducing the overall down-time. Selected data from all of the minicomputers can be sent to FDA's main computers via a digital cartridge tape recorder or paper tape. The digital cartridge tape recorder records data that are output from a minicomputer terminal and then plays it back on a terminal which is on-line with the main computer. This main computer stores and edits data; plots spectra for reports, data banks, and publications; and carries out some data processing. Multiple interfacing also serves to supplement the capabilities of the 8-year-old Finnigan MAT (formerly Varian MAT) SS-100 data system (Sperry-Univac/V-76) with the newer and more powerful Finnigan MAT INCOS (Data General/Nova 3) data system. The SS-100 data system is also enhanced by the substitution of the 110 baud paper tape with a 9600 baud cartridge tape recorder for I/O of system bootstraps, BASIC programs, and raw data. PMID:7130097

...The Food and DrugAdministration (FDA) is providing notice of a memorandum of understanding (MOU) between FDA and MEDSCAPE, LLC AND WEBMD LLC. The purpose of the MOU is to complement FDA's capacity to educate and communicate with health care professionals. It will also promote the timely dissemination to health care professionals of accurate information on public health and emerging safety......

...The Food and DrugAdministration (FDA) is announcing the availability of a draft guidance entitled ``Class II Special Controls Guidance Document: In Vitro Diagnostic Devices for Yersinia Species Detection.'' This draft guidance document describes a means by which in vitro diagnostic devices for Yersinia species (spp.) detection may comply with the requirement of special controls for class II......

This guide for administrators provides a step-by-step process for establishing new or revised policies to deal with student misuse of alcohol and other drugs on college campuses. Emphasis is on a new doctrine of environmental management which stresses the school's responsibility to take measures against foreseeable hazards and risks in the school…

... Adolescents.'' When this guidance document is final, several provisions in the Family Smoking Prevention and... Products, Food and DrugAdministration, 9200 Corporate Blvd., Rockville, MD 20850-3229. Send one self... Restricting the Sale and Distribution of Cigarettes and Smokeless Tobacco to Protect Children and...

...The Food and DrugAdministration (FDA) is announcing the availability of the draft guidance entitled ``Types of Communication During the Review of Medical Device Submissions.'' The purpose of this guidance is to update the Agency's approach to Interactive Review to reflect FDA's implementation of the Medical Device User Fee Act of 2007 (MDUFA II) Commitment Letters and of undertakings agreed......

...The Food and DrugAdministration (FDA) is announcing a publication containing modifications the Agency is making to the list of standards FDA recognizes for use in premarket reviews (FDA recognized consensus standards). This publication, entitled ``Modifications to the List of Recognized Standards, Recognition List Number: 028'' (Recognition List Number: 028), will assist manufacturers who......

...The Food and DrugAdministration (FDA) Cincinnati District, in cosponsorship with Xavier University, is announcing a public conference entitled ``FDA/Xavier University PharmaLink Conference.'' The PharmaLink conference seeks solutions to important and complicated issues by aligning with the strategic priorities of FDA, and includes presentations from key FDA officials, global regulators, and......

...): Request for Comments on the Development of a Risk-Based Regulatory Framework and Strategy for Health Information Technology AGENCY: Office of the National Coordinator for Health Information Technology...: The Food and DrugAdministration (FDA), Office of the National Coordinator for Health...

Administrators and counselors at one private and six public junior colleges in Nebraska answered questions and offered their opinions on and knowledge of drug use and abuse in their colleges. Topics covered by this study include: kinds of student involved; extent of the problem on Nebraska junior college campuses; factors that influence students…

...The Food and DrugAdministration (FDA) is announcing the availability of a draft guidance entitled ``Establishing That a Tobacco Product Was Commercially Marketed in the United States as of February 15, 2007.'' This draft guidance provides information on how a manufacturer may demonstrate that a tobacco product was commercially marketed in the United States as of February 15, 2007. In this......

...The Food and DrugAdministration (FDA) is providing notice of a Statement of Cooperation (SOC) between FDA and Secretariat of Health (SS) of the United Mexican States, through the Federal Commission for Protection from Sanitary Risks (COFEPRIS). The purpose of the SOC is to safeguard public health and to ensure the safety and sanitary quality of fresh and frozen molluscan shellfish harvested......

...The Food and DrugAdministration (FDA) is announcing the availability of the guidance entitled ``Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials.'' This guidance summarizes FDA's current thoughts on the appropriate use of Bayesian statistical methods in the design and analysis of medical device clinical...

The objective of this study was to examine C57BL/6J (B6) mice during extinction conditions, after food training, and for rates and patterns of operant behavior that seems similar to behavior maintained by intravenous cocaine injections. The rationale was to evaluate the potential for false positives in the intravenous self-administration test using protocols common in studies of knockout mice backcrossed to B6. An additional aim was to assess the influence of food-associated and drug-associated cues and mouse strain. Mice were allowed to acquire lever pressing reinforced by sweetened condensed milk under a fixed ratio 1 then fixed ratio 2 schedule of reinforcement accompanied by a flashing light. A catheter base was then implanted for simulation of intravenous self-administration conditions. Mice were allowed to lever press with cues remaining the same as during food training but without further scheduled consequences (i.e. no drug or food reinforcers delivered). All mice sustained lever pressing for several weeks, and over half met commonly used criteria for 'self-administration behavior.' Thus, B6 mice showed perseveration of a previously reinforced behavior that closely resembled rates and patterns of drug self-administration. This effect in B6 mice was greater than with A/J mice, and the lack of extinction was even more robust in the presence of cocaine-associated cues than with food-associated cues. We suggest that a necessary criterion for positive results in the intravenous drug self-administration test include an increase in responding when cocaine is made available after extinction with saline self-administration. PMID:21522054

Rationale Behavioral-economic demand curve analysis offers several useful measures of drug self-administration. Although generation of demand curves previously required multiple days, recent within-session procedures allow curve construction from a single 110-min cocaine self-administration session, making behavioral-economic analyses available to a broad range of self-administration experiments. However, a mathematical approach of curve fitting has not been reported for the within-session threshold procedure. Objectives We review demand curve analysis in drug self-administration experiments and provide a quantitative method for fitting curves to single-session data that incorporates relative stability of brain drug concentration. Methods Sprague-Dawley rats were trained to self-administer cocaine, and then tested with the threshold procedure in which the cocaine dose was sequentially decreased on a fixed ratio-1 schedule. Price points (responses/mg cocaine) outside of relatively stable brain cocaine concentrations were removed before curves were fit. Curve-fit accuracy was determined by the degree of correlation between graphical and calculated parameters for cocaine consumption at low price (Q0) and the price at which maximal responding occurred (Pmax). Results Removing price points that occurred at relatively unstable brain cocaine concentrations generated precise estimates of Q0 and resulted in Pmax values with significantly closer agreement with graphical Pmax than conventional methods. Conclusion The exponential demand equation can be fit to single-session data using the threshold procedure for cocaine self-administration. Removing data points that occur during relatively unstable brain cocaine concentrations resulted in more accurate estimates of demand curve slope than graphical methods, permitting a more comprehensive analysis of drug self-administration via a behavioral-economic framework. PMID:23086021

Background Australia is the only high income country with persisting endemic trachoma. A national control program involving mass drugadministration with oral azithromycin, in place since 2006, has some characteristics which differ from programs in low income settings, particularly in regard to the use of a wider range of treatment strategies, and more regular assessments of community prevalence. We aimed to examine the association between treatment strategies and trachoma prevalence. Methods Through the national surveillance program, annual data from 2007–2013 were collected on trachoma prevalence and treatment with oral azithromycin in children aged 5–9 years from three Australian regions with endemic trachoma. Communities were classified for each year according to one of four trachoma treatment strategies implemented (no treatment, active cases only, household and community-wide). We estimated the change in trachoma prevalence between sequential pairs of years and across multiple years according to treatment strategy using random-effects meta-analyses. Findings Over the study period, 182 unique remote Aboriginal communities had 881 annual records of both trachoma prevalence and treatment. From the analysis of pairs of years, the greatest annual fall in trachoma prevalence was in communities implementing community-wide strategies, with yearly absolute reductions ranging from -8% (95%CI -17% to 1%) to -31% (-26% to -37%); these communities also had the highest baseline trachoma prevalence (15.4%-43.9%). Restricting analyses to communities with moderate trachoma prevalence (5–19%) at initial measurement, and comparing community trachoma prevalence from the first to the last year of available data for the community, both community-wide and more targeted treatment strategies were associated with similar absolute reductions (-11% [-8% to -13%] and -7% [-5% to -10%] respectively). Results were similar stratified by region. Interpretation Consistent with previous

This paper contends that former Secretary of Education William Bennett's "war on drugs" (he now directs the government's campaign against drugs) is not being waged against those who sell and use drugs, but against the civil liberties of everyone. The paper maintains that under the guise of ridding society of what President Bush called "the…

Previous studies suggest that protective immunity against Schistosoma haematobium is primarily stimulated by antigens from dying worms. Praziquantel treatment kills adult worms, boosting antigen exposure and protective antibody levels. Current schistosomiasis control efforts use repeated mass drugadministration (MDA) of praziquantel to reduce morbidity, and may also reduce transmission. The long-term impact of MDA upon protective immunity, and subsequent effects on infection dynamics, are not known. A stochastic individual-based model describing levels of S. haematobium worm burden, egg output and protective parasite-specific antibody, which has previously been fitted to cross-sectional and short-term post-treatment egg count and antibody patterns, was used to predict dynamics of measured egg output and antibody during and after a 5-year MDA campaign. Different treatment schedules based on current World Health Organisation recommendations as well as different assumptions about reductions in transmission were investigated. We found that antibody levels were initially boosted by MDA, but declined below pre-intervention levels during or after MDA if protective immunity was short-lived. Following cessation of MDA, our models predicted that measured egg counts could sometimes overshoot pre-intervention levels, even if MDA had had no effect on transmission. With no reduction in transmission, this overshoot occurred if protective immunity was short-lived. This implies that disease burden may temporarily increase following discontinuation of treatment, even in the absence of any reduction in the overall transmission rate. If MDA was additionally assumed to reduce transmission, a larger overshoot was seen across a wide range of parameter combinations, including those with longer-lived protective immunity. MDA may reduce population levels of immunity to urogenital schistosomiasis in the long-term (3-10 years), particularly if transmission is reduced. If MDA is stopped while

Background Blinding trachoma is targeted for elimination by 2020 using the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, and Environmental improvements). Annual mass drugadministration (MDA) with azithromycin is a cornerstone of this strategy. If baseline prevalence of clinical signs of trachomatous inflammation – follicular among 1-9 year-olds (TF1-9) is ≥10% but <30%, the World Health Organization guidelines are for at least 3 annual MDAs; if ≥30%, 5. We assessed the likelihood of achieving the global elimination target of TF1-9 <5% at 3 and 5 year evaluations using program reports. Methodology/Principal Findings We used the International Trachoma Initiative’s prevalence and treatment database. Of 283 cross-sectional survey pairs with baseline and follow-up data, MDA was conducted in 170 districts. Linear and logistic regression modeling was applied to these to investigate the effect of MDA on baseline prevalence. Reduction to <5% was less likely, though not impossible, at higher baseline TF1-9 prevalences. Increased number of annual MDAs, as well as no skipped MDAs, were significant predictors of reduced TF1-9 at follow-up. The probability of achieving the <5% target was <50% for areas with ≥30% TF1-9 prevalence at baseline, even with 7 or more continuous annual MDAs. Conclusions Number of annual MDAs alone appears insufficient to predict program progress; more information on the effects of baseline prevalence, coverage, and underlying environmental and hygienic conditions is needed. Programs should not skip MDAs, and at prevalences >30%, 7 or more annual MDAs may be required to achieve the target. There are five years left before the 2020 deadline to eliminate blinding trachoma. Low endemic settings are poised to succeed in their elimination goals. However, newly-identified high prevalence districts warrant immediate inclusion in the global program. Intensified application of the SAFE strategy is needed in order to guarantee blinding

Background Scabies is endemic in many Aboriginal and Torres Strait Islander communities, with 69% of infants infected in the first year of life. We report the outcomes against scabies of two oral ivermectin mass drugadministrations (MDAs) delivered 12 months apart in a remote Australian Aboriginal community. Methods Utilizing a before and after study design, we measured scabies prevalence through population census with sequential MDAs at baseline and month 12. Surveys at months 6 and 18 determined disease acquisition and treatment failures. Scabies infestations were diagnosed clinically with additional laboratory investigations for crusted scabies. Non-pregnant participants weighing ≥15 kg were administered a single 200 μg/kg ivermectin dose, repeated after 2–3 weeks if scabies was diagnosed, others followed a standard alternative algorithm. Principal Findings We saw >1000 participants at each population census. Scabies prevalence fell from 4% at baseline to 1% at month 6. Prevalence rose to 9% at month 12 amongst the baseline cohort in association with an identified exposure to a presumptive crusted scabies case with a higher prevalence of 14% amongst new entries to the cohort. At month 18, scabies prevalence fell to 2%. Scabies acquisitions six months after each MDA were 1% and 2% whilst treatment failures were 6% and 5% respectively. Conclusion Scabies prevalence reduced in the six months after each MDA with a low risk of acquisition (1–2%). However, in a setting where living conditions are conducive to high scabies transmissibility, exposure to presumptive crusted scabies and population mobility, a sustained reduction in prevalence was not achieved. Clinical Trial Registration Australian New Zealand Clinical Trial Register (ACTRN—12609000654257). PMID:26516764

Humans and chimpanzees are the natural hosts for HIV. Non-human primate models of SIV/SHIV infection in rhesus, cynomologus and pigtail macaques have been used extensively as excellent model systems for pathogenesis and vaccine studies. However, owing to the variability of disease progression in infected macaques, a phenomenon identical to humans, coupled with their prohibitive costs, there exists a critical need for the development of small-animal models in which to study the untoward effects of HIV-1 infection. Owing to the fact that rodents are not the natural permissive hosts for lentiviral infection, development of small animal models for studying virus infection has used strategies that circumvent the steps of viral entry and infection. Such strategies involve overexpression of toxic viral proteins, SCID mice engrafted with the human PBLs or macrophages, and EcoHIV chimeric virus wherein the gp120 of HIV-1 was replaced with the gp80 of the ecotropic murine leukemia virus. Additional strategy that is often used by investigators to study the toxic effect of viral proteins involves direct stereotactic injection of the viral protein(s) into specific brain regions. The present report is a compilation of the applications of direct administration of Tat into the striatum to mimic the effects of the viral neurotoxin in the CNS. Added advantage of this model is that it is also amenable to repeated intraperitoneal cocaine injections, thereby allowing the study of the additive/synergistic effects of both the viral protein and cocaine. Such a model system recapitulates aspects of HAND in the context of drug abuse. PMID:22447295

Oral drugadministration to children poses specific pharmaceutical challenges that are often not seen to the same extent in adults, and whose occurrence may also be age dependent. When an age-appropriate dosage form is not available, manipulation of adult dosage forms (e.g., splitting and crushing of tablets or opening of capsules) has been reported as a means to facilitate administration to children. To enhance swallowability and/or mask an unpleasant taste of the dosage form to be administered, crushed/split tablets or the contents of capsules are often mixed with food or drinks or suspended in a vehicle prior to administration. However, it seems that the risks and benefits of an approach whereby the dosage form is modified prior to administration in this manner are everything but clear. The aim of the present study was to gain an overview of the physicochemical properties of a number of fluids, soft foods and suspension vehicles that are commonly reported to be mixed with oral medications before administration to children to improve patient acceptability. For this purpose, physicochemical parameters of 15 different fluids, soft foods and suspension vehicles were measured. These included pH, buffer capacity, osmolality, surface tension and viscosity. Results of the study clearly show the differences in physicochemical properties of the test candidates. It is thus obvious that the type of fluid/food mixed with a drug product before administration may have a significant impact on bioavailability of the drug administered. Therefore, a risk-based assessment of such practices considering API properties, formulation features and physicochemical properties of the fluids and foods intended to be co-administered with the dosage form, in conjunction with the anatomical and physiological maturity of the gastro-intestinal tract in the intended paediatric population, should be an essential part of paediatric oral formulation development. PMID:27183705

The recently released concept paper on Food and DrugAdministration (FDA) reform from Republican Senator, Nancy Kassebaum, is reviewed. Senator Kassebaum chairs the Senate Committee on Labor and Human Resources that will influence the Senate's action on FDA reform. The paper outlines the Senator's priorities for Congressional legislation on FDA reform in the following areas: the FDA mission and its accountability; creation of a Performance Review Panel and Industry Advisory Council; approval and access of products for seriously ill patients; the FDA's responsibility for good manufacturing practices; establishment of an Ombudsman Office for resolving disputes; dissemination of information on unapproved uses of approved products; and approval standards for new drugs. PMID:11362892

Background Since 2007 Sierra Leone has conducted mass drugadministration (MDA) for the elimination of lymphatic filariasis (LF) implemented by unpaid community health volunteers (CHVs). Other health campaigns such as Mother and Child Health Weeks (MCHW) pay for services to be implemented at community level and these persons are then known as community health workers (CHWs). In 2010, the LF MDA in the 12 districts of the Southern, Northern and Eastern Provinces un-expectantly coincided with universal distribution of Long Lasting Insecticide Treated Nets (LLITNs) during the MCHW. In-process monitoring of LF MDA was performed to ensure effective coverage was attained in hard to reach sites (HTR) in both urban and rural locations where vulnerable populations reside. Methods Independent monitors interviewed individuals eligible for LF MDA and tallied those who recalled having taken ivermectin and albendazole, calculated program coverage and reported results daily by phone. Monitoring of coverage in HTR sites in the 4 most rapidly urbanizing towns was performed after 4 weeks of LF MDA and again after 8 weeks throughout all 12 districts. End process monitoring was performed in randomly selected HTR sites not previously sampled throughout all 12 districts and compared to coverage calculated from the pre-MDA census and reported treatments. Results Only one town had reached effective program coverage (≥80%) after 4 weeks following which CHWs were recruited for LF MDA in all district headquarter towns. After 8 weeks only 4 of 12 districts had reached effective coverage so LF MDA was extended for a further month in all districts. By 12 weeks effective program coverage had been reached in all districts except Port Loko and there was no significant difference between those interviewed in communities versus households or by sex. Effective epidemiological coverage (≥65%) was reported in all districts and overall was significantly higher in males versus females. Conclusions

Background Mass drugadministration (MDA) programs have dramatically reduced lymphatic filariasis (LF) incidence in many areas around the globe, including American Samoa. As infection rates decline and MDA programs end, efficient and sensitive methods for detecting infections are needed to monitor for recrudescence. Molecular methods, collectively termed ‘molecular xenomonitoring,’ can identify parasite DNA or RNA in human blood-feeding mosquitoes. We tested mosquitoes trapped throughout the inhabited islands of American Samoa to identify areas of possible continuing LF transmission after completion of MDA. Methodology/Principle Findings Mosquitoes were collected using BG Sentinel traps from most of the villages on American Samoa's largest island, Tutuila, and all major villages on the smaller islands of Aunu'u, Ofu, Olosega, and Ta'u. Real-time PCR was used to detect Wuchereria bancrofti DNA in pools of ≤20 mosquitoes, and PoolScreen software was used to infer territory-wide prevalences of W. bancrofti DNA in the mosquitoes. Wuchereria bancrofti DNA was found in mosquitoes from 16 out of the 27 village areas sampled on Tutuila and Aunu'u islands but none of the five villages on the Manu'a islands of Ofu, Olosega, and Ta'u. The overall 95% confidence interval estimate for W. bancrofti DNA prevalence in the LF vector Ae. polynesiensis was 0.20–0.39%, and parasite DNA was also detected in pools of Culex quinquefasciatus, Aedes aegypti, and Aedes (Finlaya) spp. Conclusions/Significance Our results suggest low but widespread prevalence of LF on Tutuila and Aunu'u where 98% of the population resides, but not Ofu, Olosega, and Ta'u islands. Molecular xenomonitoring can help identify areas of possible LF transmission, but its use in the LF elimination program in American Samoa is limited by the need for more efficient mosquito collection methods and a better understanding of the relationship between prevalence of W. bancrofti DNA in mosquitoes and infection and

AIM: To investigate the nature and severity of AE related to sacral neurostimulation (SNS). METHODS: Based on Pubmed and Embase searches, we identified published trials and case series of SNS for fecal incontinence (FI) and extracted data on adverse events, requiring an active intervention. Those problems were operationally defined as infection, device removal explant or need for lead and/or generator replacement. In addition, we analyzed the Manufacturer and User Device Experience registry of the Federal DrugAdministration for the months of August - October of 2015. Events were included if the report specifically mentioned gastrointestinal (GI), bowel and FI as indication and if the narrative did not focus on bladder symptoms. The classification, reporter, the date of the recorded complaint, time between initial implant and report, the type of AE, steps taken and outcome were extracted from the report. In cases of device removal or replacement, we looked for confirmatory comments by healthcare providers or the manufacturer. RESULTS: Published studies reported adverse events and reoperation rates for 1954 patients, followed for 27 (1-117) mo. Reoperation rates were 18.6% (14.2-23.9) with device explants accounting for 10.0% (7.8-12.7) of secondary surgeries; rates of device replacement or explant or pocket site and electrode revisions increased with longer follow up. During the period examined, the FDA received 1684 reports of AE related to SNS with FI or GI listed as indication. A total of 652 reports met the inclusion criteria, with 52.7% specifically listing FI. Lack or loss of benefit (48.9%), pain or dysesthesia (27.8%) and complication at the generator implantation site (8.7%) were most commonly listed. Complaints led to secondary surgeries in 29.7% of the AE. Reoperations were performed to explant (38.2%) or replace (46.5%) the device or a lead, or revise the generator pocket (14.6%). Conservative management changes mostly involved changes in stimulation

Prescriptions for opioid analgesics to manage moderate-to-severe chronic non-cancer pain have increased markedly over the last decade. An unintentional consequence of greater prescription opioid utilization has been the parallel increase in misuse, abuse and overdose, which are serious risks associated with all opioid analgesics. In response to disturbing rises in prescription opioid abuse, the US Food and DrugAdministration (FDA) has proposed the implementation of aggressive Risk Evaluation and Mitigation Strategies (REMS). While REMS could dramatically change the development, release, marketing and prescription of extended-release opioids, questions remain on how these programmes may influence prescribing practices, patient safety and ultimately patient access to these agents. The extent of the availability and misuse of prescription opioids in Europe is difficult to assess from the data currently available, due in large part to the considerable differences in prescribing patterns and regulations between countries. Balancing the availability of prescription opioids for those patients who have pain, while discouraging illicit use, is a complex challenge and requires effective efforts on many levels, particularly in Europe where policies are quite different between countries. PMID:23116252

The growing interest in the composition and effects of microbiota raised the question how drug pharmacokinetics could be influenced by concomitant application of probiotics. The aim of this study was to find whether probiotic E. coli strain Nissle 1917 (EcN) influences the pharmacokinetics of concomitantly taken antiarrhythmic drug amiodarone (AMI). Live bacterial suspension of probiotic EcN (or non-probiotic E. coli strain ATCC 25922) was applied orally to male Wistar rats for seven days, while a control group of rats was treated with a saline solution. On the eighth day, the amiodarone hydrochloride was administered as one single oral dose (50 mg/kg) to all rats (N = 60). After 0, 1, 2, 3, 4, 5.5, 7, 9, 14, 22, and 30 hours, blood samples were taken from the rat abdominal aorta. The plasma level of AMI and its metabolite N-desethylamiodarone (DEA) was determined using the HPLC with UV detection. Administration of EcN led to a 43% increase of AMI AUC0-30 in comparison with control samples. However, this effect was not observed if EcN was replaced by a reference non-probiotic E. coli strain. Thus, EcN administration was most probably responsible for better drug absorption from the gastrointestinal tract. Plasma levels of DEA were also increased in plasma samples from animals treated with EcN. This change was again not found in the experiment with the reference non-probiotic strain. Higher DEA levels in samples from EcN-treated rats may be explained either by better absorption of AMI and/or by an increased activity of CYP2C forms, known to participate in metabolism of this drug, after EcN administration. In this paper, it is documented that concomitantly taken probiotic EcN may modulate pharmacokinetics of a drug; in this case, it led to an increased bioavailability of AMI. PMID:24505278

... Administration and the International Anesthesia Research Society for the Strategies for Mitigating Anesthesia... memorandum of understanding (MOU) 222-09-0014 between the International Anesthesia Research Society...

This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity--properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administration, GPEI could not be magnetically accumulated in tumors of rats harboring orthotopic 9L-gliosarcomas due to its poor pharmacokinetic properties, reflected by a negligibly low plasma AUC of 12 +/- 3 microg Fe/ml min. To improve "passive" GPEI presentation to brain tumor vasculature for subsequent "active" magnetic capture, we examined the intra-carotid route as an alternative for nanoparticle administration. Intra-carotid administration in conjunction with magnetic targeting resulted in 30-fold (p=0.002) increase in tumor entrapment of GPEI compared to that seen with intravenous administration. In addition, magnetic accumulation of cationic GPEI (zeta-potential = + 37.2 mV) in tumor lesions was 5.2-fold higher (p=0.004) than that achieved with slightly anionic G100 (zeta-potential= -12 mV) following intra-carotid administration, while no significant accumulation difference was detected between the two types of nanoparticles in the contra-lateral brain (p=0.187). These promising results warrant further investigation of GPEI as a potential cell-permeable, magnetically-responsive platform for brain tumor delivery of drugs and genes. PMID:20494439

This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity – properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administration, GPEI could not be magnetically accumulated in tumors of rats harboring orthotopic 9L-gliosarcomas due to its poor pharmacokinetic properties, reflected by a negligibly low plasma AUC of 12 ± 3 μg Fe/ml*min. To improve “passive” GPEI presentation to brain tumor vasculature for subsequent “active” magnetic capture, we examined the intra-carotid route as an alternative for nanoparticle administration. Intra-carotid administration in conjunction with magnetic targeting resulted in 30-fold (p = 0.002) increase in tumor entrapment of GPEI compared to that seen with intravenous administration. In addition, magnetic accumulation of cationic GPEI (ζ-potential = + 37.2 mV) in tumor lesions was 5.2-fold higher (p = 0.004) than that achieved with slightly anionic G100 (ζ-potential = −12 mV) following intra-carotid administration, while no significant accumulation difference was detected between the two types of nanoparticles in the contra-lateral brain (p = 0.187). These promising results warrant further investigation of GPEI as a potential cell-permeable, magnetically-responsive platform for brain tumor delivery of drugs and genes. PMID:20494439

Introduction Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination. Methods This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1–14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test. Results A total of 1,284 children were enrolled in the study. Amongst children aged 5–14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6–47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1–8.7%), and this did not differ significantly from our initial post-mass drugadministration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1–4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6–7.1%). This did not differ significantly from the

Abstract. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) includes communitywide treatment in areas with ≥ 25% prevalence of schistosomiasis along the shores of Lake Victoria using community health workers (CHWs). The CHWs are key drivers in community-owned mass drugadministration (MDA) intervention programs. We explored their experiences and perceptions after initial MDA participation. Unstructured open-ended group discussions were conducted after completion of MDA activities. Narratives were obtained from CHWs using a digital audio recorder during the group discussion, transcribed verbatim and translated into English where applicable. Thematic decomposition of data was done using ATLAS.t.i. software. From the perspective of the CHWs, factors influencing MDA compliance included drug side effects, food supply stability, and conspiracy theories about the "real" purpose of treatment. The interest of CHWs to serve as community drug distributors stemmed from both intrinsic and extrinsic factors. Feedback from CHWs can promote more effective MDA in rural Kenyan communities. PMID:23091190

In 2007, the Food and DrugAdministration requested that manufacturers of all approved gadolinium-based contrast agents (GBCAs), drugs widely used in magnetic resonance imaging, use nearly identical text in their product labeling to describe the risk of nephrogenic systemic fibrosis (NSF). Accumulating information about NSF risks led to revision of the labeling text for all of these drugs in 2010. The present report summarizes the basis and purpose of this class-labeling approach and describes some of the related challenges, given the evolutionary nature of the NSF risk evidence. The class-labeling approach for presentation of product risk is designed to decrease the occurrence of NSF and to enhance the safe use of GBCAs in radiologic practice. PMID:22923714

The mathematical modeling of physical and biologic systems represents an interesting alternative to study the behavior of these phenomena. In this context, the development of mathematical models to simulate the dynamic behavior of tumors is configured as an important theme in the current days. Among the advantages resulting from using these models is their application to optimization and inverse problem approaches. Traditionally, the formulated Optimal Control Problem (OCP) has the objective of minimizing the size of tumor cells by the end of the treatment. In this case an important aspect is not considered, namely, the optimal concentrations of drugs may affect the patients' health significantly. In this sense, the present work has the objective of obtaining an optimal protocol for drugadministration to patients with cancer, through the minimization of both the cancerous cells concentration and the prescribed drug concentration. The resolution of this multi-objective problem is obtained through the Multi-objective Optimization Differential Evolution (MODE) algorithm. The Pareto's Curve obtained supplies a set of optimal protocols from which an optimal strategy for drugadministration can be chosen, according to a given criterion. PMID:27265048

Currently, as there is no systematic norm or standard for drug safety and inspection, it cannot be judged whether the regulatory authority or regulators have fulfilled their administrative responsibilities entirely or not, when a drug safety-related incident occurs. And there is a probability that some may even be wrongly punished. In this study, we have analyzed the risk of not having appropriate norms in place and also put forward recommendations for the government or the regulatory authorities to set up norms to be fulfilled for drug safety and inspection issues. This, on one hand, could provide a basic guideline for the regulatory authorities and regulators to improve their professional levels and administrative acumen and on the other hand, it could also provide a baseline for society to judge whether the regulatory authorities and regulators have fulfilled their responsibilities correctly and thereby also help prevent regulators from being mistakenly punished. This study proposes that a systematic and functional norm for drug safety and inspection could be set up relating to the determination of the responsibilities of regulatory authorities and scope of various inspections, number and frequency of inspections, number and qualifications of regulators, handling of inspection results, inspection records, and disciplinary codes for inspectors. This study also puts forward suggestions on who should be responsible for drafting the norms and what are the factors that need to be considered while formulating the norms. PMID:27352264

We have recently reported that the endogenous mGlu2/3 agonist N-acetylaspartylglutamate (NAAG) and the N-acetylated-alpha-linked-acidic dipeptidase (NAALADase, a NAAG degradation enzyme) inhibitor 2-PMPA significantly inhibit cocaine self-administration and cocaine-induced reinstatement of drug-seeking behavior by attenuating cocaine-enhanced extracellular dopamine and glutamate in the nucleus accumbens. However, the poor oral bioavailability of NAAG and 2-PMPA limits their practical use in humans. In the present study, we investigated the effects of the orally active NAALADase inhibitor GPI-5693 and its enantiomers on cocaine-taking and cocaine-seeking behaviours. We found that oral administration of GPI-5693 (15, 30, 60 mg/kg, p.o.) did not significantly alter intravenous cocaine self-administration under fixed-ratio (FR2) reinforcement, but significantly inhibited cocaine-induced reinstatement of the extinguished drug-seeking behavior. This inhibition was blocked by pretreatment with LY341495, a selective mGlu2/3 receptor antagonist. Pretreatment with the same doses (15, 30, 60 mg/kg, p.o.) of GPI-16476 or GPI-16477, two enantiomers of GPI-5693, also inhibited cocaine-induced reinstatement similar to GPI-5693. In contrast, GPI-5693 altered neither oral sucrose self-administration nor sucrose-triggered reinstatement of sucrose-seeking behavior. These data suggest that orally effective NAAG peptidase inhibitors deserve further study as potential agents for the treatment of cocaine addiction. PMID:19887067

Treatment for persistent pulmonary hypertension of the newborn (PPHN) aims to reduce pulmonary vascular resistance while maintaining systemic vascular resistance. Selective pulmonary vasodilation may be achieved by targeting pulmonary-specific pathways or by delivering vasodilators directly to the lungs. Abrupt withdrawal of a pulmonary vasodilator can cause rebound pulmonary hypertension. Therefore, use of consistent delivery systems that allow for careful monitoring of drug delivery is important. This manuscript reviews published studies of inhaled vasodilators used for treatment of PPHN and provides an overview of safety issues associated with drug delivery and delivery devices as they relate to the risk of rebound pulmonary hypertension. Off-label use of aerosolized prostacyclins and an aerosolized prostaglandin in neonates with PPHN has been reported; however, evidence from large randomized clinical trials is lacking. The amount of a given dose of aerosolized drug that is actually delivered to the lungs is often unknown, and the actual amount of drug deposited in the lungs can be affected by several factors, including patient size, nebulizer used, and placement of the nebulizer within the breathing circuit. Inhaled nitric oxide (iNO) is the only pulmonary vasodilator approved by the US Food and DrugAdministration for the treatment of PPHN. The iNO delivery device, INOmax DSIR®IR, is designed to constantly monitor NO, NO2, and O2 deliveries and is equipped with audible and visual alarms to alert providers of abrupt discontinuation and incorrect drug concentration. Other safety features of this device include two independent backup delivery systems, a backup drug cylinder, a battery that provides up to 6 hours of uninterrupted medication delivery, and 27 alarms that monitor delivery, dosage, and system functions. The ability of the drug delivery device to provide safe, consistent dosing is important to consider when selecting a pulmonary vasodilator. PMID

Treatment for persistent pulmonary hypertension of the newborn (PPHN) aims to reduce pulmonary vascular resistance while maintaining systemic vascular resistance. Selective pulmonary vasodilation may be achieved by targeting pulmonary-specific pathways or by delivering vasodilators directly to the lungs. Abrupt withdrawal of a pulmonary vasodilator can cause rebound pulmonary hypertension. Therefore, use of consistent delivery systems that allow for careful monitoring of drug delivery is important. This manuscript reviews published studies of inhaled vasodilators used for treatment of PPHN and provides an overview of safety issues associated with drug delivery and delivery devices as they relate to the risk of rebound pulmonary hypertension. Off-label use of aerosolized prostacyclins and an aerosolized prostaglandin in neonates with PPHN has been reported; however, evidence from large randomized clinical trials is lacking. The amount of a given dose of aerosolized drug that is actually delivered to the lungs is often unknown, and the actual amount of drug deposited in the lungs can be affected by several factors, including patient size, nebulizer used, and placement of the nebulizer within the breathing circuit. Inhaled nitric oxide (iNO) is the only pulmonary vasodilator approved by the US Food and DrugAdministration for the treatment of PPHN. The iNO delivery device, INOmax DSIR®IR, is designed to constantly monitor NO, NO2, and O2 deliveries and is equipped with audible and visual alarms to alert providers of abrupt discontinuation and incorrect drug concentration. Other safety features of this device include two independent backup delivery systems, a backup drug cylinder, a battery that provides up to 6 hours of uninterrupted medication delivery, and 27 alarms that monitor delivery, dosage, and system functions. The ability of the drug delivery device to provide safe, consistent dosing is important to consider when selecting a pulmonary vasodilator. PMID

Over the past decade, personalized medicine has received considerable attention from researchers, drug developers, and regulatory agencies. Personalized medicine includes identifying patients most likely to benefit and those most likely to experience adverse reactions in response to a drug, and tailoring therapy based on pharmacokinetics or pharmacodynamic response, as well. Perhaps most exciting is finding ways to identify likely responders through genetic, proteomic, or other tests, so that only likely responders will be treated. However, less precise methods such as identifying historical, demographic, or other indicators of increased or reduced responsiveness are also important aspects of personalized medicine. The cardiovascular field has not used many genetic or proteomic markers, but has regularly used prognostic variables to identify likely responders. The development of biomarker-based approaches to personalized medicine in cardiovascular disease has been challenging, in part, because most cardiovascular therapies treat acquired syndromes, such as acute coronary syndrome and heart failure, which develop over many decades and represent the end result of several pathophysiological mechanisms. More precise disease classification and greater understanding of individual variations in disease pathology could drive the development of targeted therapeutics. Success in designing clinical trials for personalized medicine will require the selection of patient populations with attributes that can be targeted or that predict outcome, and the use of appropriate enrichment strategies once such attributes are identified. Here, we describe examples of personalized medicine in cardiovascular disease, discuss its impact on clinical trial design, and provide insight into the future of personalized cardiovascular medicine from a regulatory perspective. PMID:26459078

The Food and DrugAdministration (FDA) is further delaying, until December 1, 2006, the effective date of certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). In the Federal Register of May 3, 2000 (65 FR 25639), the agency delayed until October 1, 2001, the effective date of certain requirements in the final rule relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record, and distribution of blood derivatives by entities that meet the definition of a "health care entity" in the final rule. The agency further delayed the effective date of these requirements in three subsequent Federal Register notices. Most recently, in the Federal Register of January 31, 2003 (68 FR 4912), FDA delayed the effective date until April 1, 2004. This action further delays the effective date of these requirements until December 1, 2006. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and DrugAdministration Modernization Act of 1997 (the Modernization Act). The agency is taking this action to address concerns about the requirements in the final rule raised by affected parties. As explained in the SUPPLEMENTARY INFORMATION section, FDA is working with stakeholders through its counterfeit drug initiative to facilitate widespread, voluntary adoption of track and trace technologies that will generate a de facto electronic pedigree, including prior transaction history back to the original manufacturer, as a routine course of business. If this technology is widely adopted, it is expected to help fulfill the pedigree requirements of the PDMA and obviate or resolve many of the concerns that have been raised with respect to the final rule by ensuring that an electronic pedigree travels with a drug product at all times. Therefore, it is necessary to delay the effective date of Sec

It comes as no surprise to those in the underground that thalidomide, a TNF-inhibitor, is still defined by its teratogenicity, or ability to cause birth defects. In the late 1950s, thousands of babies were born with horrific birth defects after a company started marketing the drug as safe for morning sickness. Forty years later, after three double blind placebo-controlled studies, numerous case studies, and hundreds of anecdotal reports from doctors treating oral and throat ulcers, the drug is still in clinical trials, and not yet available to treat AIDS-relatetd wasting. Pilot studies of the drug show significant weight gain for patients. In addition, the drug is inexpensive and offers a specific mechanism of inhibiting an inflammatory chemical called TNF-alpha, the substance which presumably aggravates weight loss in people with AIDS. The Underground Thalidomide Compassionate Use Program will begin providing thalidomide as soon as they can secure a safe pharmaceutical supply. PMID:11362280

Data reported directly by patients about how they feel and function are rarely included in oncology drug labeling in the United States, in contrast to Europe and to nononcology labeling in the United States, where this practice is more common. Multiple barriers exist, including challenges unique to oncology trials, and industry's concerns regarding cost, logistical complexities, and the Food and DrugAdministration's (FDA's) rigorous application of its 2009 guidance on the use of patient-reported outcome (PRO) measures. A panel consisting of representatives of industry, FDA, the PRO Consortium, clinicians, and patients was assembled at a 2014 workshop cosponsored by FDA to identify practical recommendations for overcoming these barriers. Key recommendations included increasing proactive encouragement by FDA to clinical trial sponsors for including PROs in drug development programs; provision of comprehensive PRO plans by sponsors to FDA early in drug development; promotion of an oncology-specific PRO research agenda; development of an approach to existing ("legacy") PRO measures, when appropriate (focused initially on symptoms and functional status); and increased FDA and industry training in PRO methodology. FDA has begun implementing several of these recommendations. PMID:26181187

P-Glycoprotein (P-gp) mediated efflux is recognized as a significant biochemical barrier affecting oral absorption for a number of drugs. Various conflicting reports have been published regarding the effects of grapefruit juice (GFJ) on P-gp-mediated drug efflux, in which GFJ has been shown both to inhibit and activate it. Hence, the present study adopted a two-way approach, involving both co-treatment and chronic administration. Bi-directional transport of paclitaxel (PCL) was carried out in the absence and presence of GFJ extract, in rat everted ileum sac. Further, the effect of chronic administration of GFJ to rats was characterized by permeability studies with indinavir (INDI). Co-treatment of GFJ extract at 100% concentration reduced the asymmetric transport of PCL (efflux ratio = 20.8) by increasing absorptive (A --> B) transport by 921% and reducing secretory (B --> A) transport by 41%. Further, GFJ showed a concentration dependent effect on PCL permeability. Imipramine, a passive permeability marker with absorptive permeability of 15.33 +/- 4.26 x 10(-6) cm/s showed no asymmetric transport and also no significant (P < 0.05) change in permeability in the presence of GFJ. Chronic administration of GFJ resulted in a significant decrease in absorptive transport of indinavir, which was even greater than that produced by rifampicin pretreatment. No change in permeability of propranolol, a passive permeability marker, was observed. Further, the decrease in absorptive transport of INDI was reversed by the P-gp inhibitor verapamil. In conclusion, GFJ extract inhibited P-gp-mediated efflux in co-treatment, whereas chronic administration led to increased levels of P-gp expression, thus having a profound effect on intestinal absorption and GFJ-drug interactions in vivo. PMID:16398269

Drug addiction is associated with altered dopamine (DA) neurotransmission in the basal ganglia. We have previously shown that chronic stimulation of the dopamine D2 receptor (D(2)R) with cocaine results in reduced striatal DA terminal density. The aims of this study were to establish whether this reduction in DA terminal density results in reduced striatal DA release and increased cocaine-seeking behaviour and whether D(2)R antagonism can restore the cocaine-induced alterations in DA neurotransmission and drug-seeking behaviour. Rats were housed individually and either control, cocaine, haloperidol (D(2)R antagonist), or cocaine and haloperidol was administered in the drinking water for 16 weeks. Chronic cocaine treatment, which reduced striatal DA terminal density by 20%, resulted in a reduction in basal (-34%) and cocaine-evoked (-33%) striatal DA release and increased cocaine-seeking behaviour. These cocaine-mediated effects on striatal DA terminal density, DA release and drug-seeking could be prevented by co-administration with haloperidol. Basal and cocaine-evoked DA release in the striatum directly correlated with DA terminal density and with preference for cocaine. We conclude that striatal DA terminal density and DA release is an important factor in maintaining drug preference and should be considered as a factor in drug-seeking behaviour and relapse. PMID:21129449

The objective of this paper was to review existing information regarding food effects on drug absorption within paediatric populations. Mechanisms that underpin food–drug interactions were examined to consider potential differences between adult and paediatric populations, to provide insights into how this may alter the pharmacokinetic profile in a child. Relevant literature was searched to retrieve information on food–drug interaction studies undertaken on: (i) paediatric oral drug formulations; and (ii) within paediatric populations. The applicability of existing methodology to predict food effects in adult populations was evaluated with respect to paediatric populations where clinical data was available. Several differences in physiology, anatomy and the composition of food consumed within a paediatric population are likely to lead to food–drug interactions that cannot be predicted based on adult studies. Existing methods to predict food effects cannot be directly extrapolated to allow predictions within paediatric populations. Development of systematic methods and guidelines is needed to address the general lack of information on examining food–drug interactions within paediatric populations. PMID:27417362

... automobile accident reparations insurance. This updated administrative cost charge was effective on January 1...-connected disability incurred as a result of a motor vehicle accident in a State that requires...

... Administration's (FDA) Office of Orphan Products Development is announcing the following workshop: FDA Pediatric... Office of Orphan Product Development and will include participants from the FDA's Center for Devices...

The parenteral administration of combinations of drugs is often necessary in palliative medicine, particularly in the terminal stage of life, when patients are no longer able to take medication orally. The use of infusers to administer continuous subcutaneous infusions is a well-established practice in the palliative care setting and enables several drugs to be given simultaneously, avoiding the need for repeated administrations and the effects of peaks and troughs in the doses of medication. The method is also appreciated by patients and caregivers in the home care setting because the devices and infusion sites are easy to manage. Despite their frequent use, however, the mixtures of drugs adopted in clinical practice are sometimes not supported by reliable data concerning their chemical and physical compatibility. The present study investigates the chemical compatibility of binary mixtures (morphine with ketorolac) and the physical compatibility of binary (morphine or methadone with ketorolac) or ternary mixtures (morphine with ketorolac and/or haloperidol, and/or dexamethasone, and/or metoclopramide, and/or hyoscine butylbromide) with a view to reducing the aleatory nature of the empirical use of such combinations, thereby increasing their safety and clinical appropriateness. PMID:22252547

Background Irinotecan-loaded drug-eluting beads represent a novel drug delivery method that allows for the locoregional delivery of irinotecan to colorectal liver metastases (CRLM). The method has shown impressive response rates. However, the pathological response to this treatment has not previously been demonstrated. Methods Patients with easily resectable CRLM were treated with drug-eluting beads delivering irinotecan (DEBIRI) 4 weeks prior to resection. Pathological tumour response was graded using a validated system. The intraoperative detection of previously unidentified disease allowed for the assessment of pathological responses directly attributable to bead treatment. Results In Patient 1, segmental embolization of the target lesion in segment VIII resulted in 100% necrosis (0% viability). An untreated lesion in segment IV was found to be 30% viable. In Patient 2, subsegmental embolization of the target lesion in segment VI resulted in 60% necrosis and 40% fibrosis (0% viability). An untreated lesion in segment VI remained 60% viable. In Patient 3, lobar embolization of the target lesion in segment II resulted in 0% viability. Two further lesions within the treated hemiliver, both with 0% viability, and one lesion in the untreated hemiliver with 45% viability were discovered at laparotomy. Conclusions This series demonstrates the effectiveness of DEBIRI in the treatment of CRLM. High rates of tumour destruction are possible, even with the proximal lobar administration of DEBIRI. Lobar administration appears to be an appropriate method of delivery for integration into future therapeutic regimens. PMID:23216781

The conduct of a clinical investigation of a medical device to determine the safety and effectiveness of the device is covered by the investigational device exemptions (IDE) regulation. The purpose of IDE regulation is "to encourage, to the extent consistent with the protection of public health and safety and with ethical standards, the discovery and development of useful devices intended for human use, and to that end to maintain optimum freedom for scientific investigators in their pursuit of this purpose" (Federal Food, Drug, and Cosmetic Act). Conducting a clinical investigation may require an approved IDE application. The US Food and DrugAdministration encourages early interaction with the agency through the pre-IDE process during the development of a device or technology and during the preparation of an IDE application. This facilitates approval of the IDE application and progression into the clinical investigation. This paper reviews the terminology and applicability of the IDE regulation and the type of study that requires an IDE application to the Food and DrugAdministration. The pre-IDE process and the development of an IDE application for a significant risk study of a cardiovascular device are discussed. PMID:10069924

The Food and DrugAdministration (FDA or Agency) is issuing a regulation to establish a list of "qualifying pathogens'' that have the potential to pose a serious threat to public health. This final rule implements a provision of the Generating Antibiotic Incentives Now (GAIN) title of the Food and DrugAdministration Safety and Innovation Act (FDASIA). GAIN is intended to encourage development of new antibacterial and antifungal drugs for the treatment of serious or life-threatening infections, and provides incentives such as eligibility for designation as a fast-track product and an additional 5 years of exclusivity to be added to certain exclusivity periods. Based on analyses conducted both in the proposed rule and in response to comments to the proposed rule, FDA has determined that the following pathogens comprise the list of ``qualifying pathogens:'' Acinetobacter species, Aspergillus species, Burkholderia cepacia complex, Campylobacter species, Candida species, Clostridium difficile, Coccidioides species, Cryptococcus species, Enterobacteriaceae (e.g., Klebsiella pneumoniae), Enterococcus species, Helicobacter pylori, Mycobacterium tuberculosis complex, Neisseria gonorrhoeae, N. meningitidis, Non-tuberculous mycobacteria species, Pseudomonas species, Staphylococcus aureus, Streptococcus agalactiae, S. pneumoniae, S. pyogenes, and Vibrio cholerae. The preamble to the proposed rule described the factors the Agency considered and the methodology used to develop the list of qualifying pathogens. As described in the preamble of this final rule, FDA applied those factors and that methodology to additional pathogens suggested via comments on the proposed rule. PMID:24908687

To reduce the high rate of human immunodeficiency virus (HIV) infection among intravenous drug users in Nepal, the Lifesaving and Lifegiving Society of Kathmandu has been distributing sterile injecting equipment in exchange for contaminated materials since 1991. In addition, community health outreach workers affiliated with the program provide condoms and bleach, HIV counseling and education, and primary health care to about 750 of the estimated 1500-2000 intravenous drug users in the Kathmandu valley. Of the 48,386 client contacts in 1991-94, over half involved syringe exchange. During this period, 586 randomly selected clients were selected for interviews and serologic testing. The number of times drug users shared equipment declined from 14 times per week in the 1991 subsample to once a day or less in the 1993 and 1994 subsamples. Knowledge of HIV infection rose from 58% in 1991 to almost 100% in 1994, while the proportion of drug users considering themselves at risk of HIV increased from 25% to 47%. There were no significant changes in HIV seropositivity (1.6% in 1991) during the study period, and no new cases were recorded in 1993 or 1994. This finding confirms the effectiveness of needle/syringe exchange programs in controlling the spread of HIV infection among intravenous drug users. PMID:8527080

This study aimed to identify the cause of atypical shape of measured concentration-time profile in the peak area by one compartment open model with a lag time (Bateman function with a lag) after single dose oral administration of drug published in "Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Application" by Gabrielsson and Weiner (1997) and two concentration profiles after frequent sampling oral glucose tolerance test. Following the oral administration of 100 μg of substance A to human volunteer, frequent sampling was carried out and concentration-time profiles were obtained. Our hemodynamic circulatory structural model capable of parameters estimation of circulation and gastrointestinal subsystem to explain the plateau within the interval 40-100 min (substance A) and 15-30 min (glucose) of the measured concentration-time profile was developed. The mean residence time, the rate constants of absorption and elimination parameters of our model were calculated. Comparing to the Bateman function, our results demonstrate better approximation of the substance A and glucose concentration-time profile and estimation of absorption rate constant by our structural model. Obtained model results indicate that the atypical shape of measured concentration-time profile of single dose oral administration of drug was probably caused by the gastrointestinal and circulation system with deep compartment. This applies to the substances with high coefficient of absorption. PMID:24019565

Question A child in my clinic who recently sprained his ankle is experiencing pain and having trouble bearing weight on the affected leg. His mother has been giving him acetaminophen, as she was told never to use nonsteroidal anti-inflammatory drugs (NSAIDs) because of his pharmacologically controlled asthma. Is asthma in children a contraindication to giving NSAIDs? Is NSAID-exacerbated respiratory disease (NERD) a real entity? Answer Nonsteroidal anti-inflammatory drugs are effective analgesic and antipyretic medications. While described in adults with some predisposing conditions, NERD has not been clearly described in a large number of children. Nonsteroidal anti-inflammatory drugs can be recommended to children with known wheeze who do not have a history of NERD reaction. PMID:27521389

Infestation by geohelminths is an important public health problem in developing countries like India. It is a major cause of morbidity in school-age children who have the highest burden of worm infestation. Some of the morbid conditions attributed to intestinal helminthiasis are malnutrition, growth retardation, anaemia, vitamin A deficiency and impaired intellectual performance. Chemotherapy targeted at school-age children has been recommended as a cost-effective and feasible control programme for the control of geohelminths. To optimize resources a geohelminth control programme can be integrated with other existing national health programmes. The availability of drugs such as diethyl carbamazine (DEC) and albendazole, which have anthelminthic and antifilarial properties, opens the possibility of integrating a geohelminth control programme with a filaria control programme. However, co-administration of DEC and albendazole raises several issues of frequency of administration, efficacy, compliance and cost-effectiveness. Thus, integrating a geohelminth control programme with the existing mid-day meal or anaemia prophylaxis programme would be a more appropriate and cost-effective strategy to control geohelminths, alleviate the morbidity caused by them and improve the overall health of the community. PMID:11467143

Background Mass drugadministration (MDA) of antibiotics is a key component of the so-called “SAFE” strategy for trachoma control, while MDA of anthelminthics provides the cornerstone for control of a number of other neglected tropical diseases (NTDs). Simultaneous delivery of two or more of these drugs, renowned as “integrated NTD control,” is being promoted to reduce costs and expand intervention coverage. A cost analysis was conducted alongside an MDA campaign in a remote trachoma endemic area, to inform budgeting for NTD control in South Sudan. Methods and Findings A first round of antibiotic MDA was conducted in the highly trachoma endemic county of Mayom, Unity state, from June to August 2010. A core team of seven staff delivered the intervention, including recruitment and training of 44 supervisors and 542 community drug distributors. Using an ingredients approach, financial and economic costs were captured from the provider perspective in a detailed costing database. Overall, 123,760 individuals were treated for trachoma, resulting in an estimated treatment coverage of 94%. The economic cost per person treated was USD 1.53, excluding the cost of the antibiotic azithromycin. Ninety four per cent of the delivery costs were recurrent costs, with personnel and travel/transport costs taking up the largest share. Conclusions In a remote setting and for the initial round, MDA of antibiotics was considerably more expensive than USD 0.5 per person treated, an estimate frequently quoted to advocate for integrated NTD control. Drug delivery costs in South Sudan are unlikely to decrease substantially during subsequent MDA rounds, as the major cost drivers were recurrent costs. MDA campaigns for delivery of one or more drugs in South Sudan should thus be budgeted at around USD 1.5 per person treated, at least until further costing data for delivery of other NTD drugs, singly or in combination, are available. PMID:22022632

...The Office of Management and Budget (OMB) is consolidating all Federal regulations concerning drug-free workplace requirements for recipients of financial assistance. Accordingly, we are removing our regulation on this subject currently located within title 20 of the Code of Federal Regulations (CFR) and issuing a new regulation to adopt the OMB guidance at 2 CFR part 182. The new regulation......

... Under a BLA, NDA, or PMA.'' This draft guidance intends to provide the underlying principles to... new drug application (NDA), or a device premarket approval application (PMA). DATES: Although you can..., or PMA.'' This document provides guidance to industry and FDA staff on the underlying principles...

... manufacturing operations with information on a number of topics concerning FDA requirements and expectations related to current good manufacturing practice (CGMP). The joint public workshop offers the opportunity... Network; (4) IT Strategies--Cloud Computing, RFID, and Beyond; (5) The Future of Drug Manufacturing....

The Food and DrugAdministration (FDA) is amending its classification regulations to designate class I devices that are exempt from the premarket notification requirements, subject to certain limitations, and to designate those class I devices that remain subject to premarket notification requirements under the new statutory criteria for premarket notification requirements. The devices FDA is designating as exempt do not include class I devices that have been previously exempted by regulation from the premarket notification requirements. This action is being taken under the Federal Food, Drug, and Cosmetic Act (the act), as amended by the Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 (SMDA), and the FDA Modernization Act of 1997 (FDAMA). FDA is taking this action in order to implement a requirement of FDAMA. Elsewhere in this issue of the Federal Register, FDA is announcing that it is withdrawing proposed rules to revoke existing exemptions from premarket notification for two devices. PMID:11010655

Under Food and DrugAdministration (FDA) policy, communications by prescription drug manufacturers must be backed by "substantial evidence" from "adequate and well-controlled investigations." But numerous exceptions permit manufacturer promotion based on data other than randomized trials. The observational research presented in the Hemikrane hypothetical case in this month's Health Affairs is methodologically flawed and also does not meet any of these exceptions. Therefore, plausible scientific and policy rationales support rules restricting the company's communication of its findings. The FDA's current reluctance to authorize promotional claims based on observational research is understandable. Further work is required to define the characteristics of high-quality observational research. However, as this field matures, higher-quality observational studies could meet the legal standard of an "adequate and well-controlled investigation." At that point, the FDA will need to issue formal guidance to minimize confusion on what kinds of observational research can meet its evidentiary standards. PMID:23048097

Radiation induced white matter necrosis in the rat spinal cord is preceded by changes in permeability of the blood brain-barrier, reduced blood flow, and infarction so that the necrosis is an ischemic necrosis. Attempts have been made to modify this developing pathology by the administration of drugs post-irradiation but just prior to the changes in vascular permeability. Verapamyl, a calcium channel blocker, had no effect on the development of ataxia. Dipyridamole, a drug which increases blood flow and reduces thrombosis, delayed and reduced the onset of ataxia. A low iron diet and desferrioxamine which reduces reperfusion injury also delayed and reduced ataxia. These results support the thesis that vascular changes are an important pathway in the development of radiation necrosis and that reperfusion injury is an important factor in the development and exacerbation of radiation damage to the spinal cord.

Examines drug-prevention programs in the United Kingdom and the United States which have included parents within their intervention strategies. Reviews implications for practice, describes a small number of model programs, and identifies critical issues for policy and practice regarding identifying, recruiting, and retaining parents within the…

In central Nigeria Anopheles mosquitoes transmit malaria and lymphatic filariasis (LF). The strategy used for interrupting LF transmission in this area is annual mass drugadministration (MDA) with albendazole and ivermectin, but after 8 years of MDA, entomological evaluations in sentinel villages showed continued low-grade mosquito infection rates of 0.32%. After long-lasting insecticidal net (LLIN) distribution by the national malaria program in late 2010, however, we were no longer able to detect infected vectors over a 24-month period. This is evidence that LLINs are synergistic with MDA in interrupting LF transmission. PMID:24205421

We previously observed, using in vivo microdialysis, that the potassium-evoked release of frontocortical serotonin (5-HT) is suppressed after rats receive high doses (30 mg/kg, i.p., daily for 3 days) of fluoxetine, a selective blocker of 5-HT reuptake. We now describe similar impairments in 5-HT release after repeated administration of two other 5-HT uptake blockers, zimelidine and sertraline (both at 20 mg/kg, i.p. for 3 days) as well as after dexfenfluramine (7.5 mg/kg, i.p. daily for 3 days), a drug which both releases 5-HT and blocks its reuptake. Doses of these indirect serotonin agonists were about 4-6 times the drug's ED50 in producing anorexia, a serotonin-related behavior. In addition, methiothepin (20 microM), a non-selective receptor antagonist, locally perfused through the dialysis probe 24 h after the last drug injection, enhanced K(+)-evoked release of 5-HT at serotoninergic nerve terminals markedly in control rats and slightly in rats treated with high doses of dexfenfluramine or fluoxetine. On the other hand, pretreatment with methiothepin (10 mg/kg, i.p.) one hour before each of the daily doses of fluoxetine or dexfenfluramine given for 3 days, totally prevented the decrease in basal and K(+)-evoked release of 5-HT. Finally, when methiothepin was injected systemically the day before the first of 3 daily injections of dexfenfluramine, it partially attenuated the long-term depletion of brain 5-HT and 5-HIAA levels induced by repeated administration of high doses of dexfenfluramine. These data suggest that drugs which bring about the prolonged blockade of 5-HT reuptake - such as dexfenfluramine and fluoxetine - can, by causing prolonged increases in intrasynaptic 5-HT levels as measured by in vivo microdialysis, produce receptor-mediated long-term changes in the processes controlling serotonin levels and dynamics.

... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND... Administration, United States Department of Health and Human Services and the Association of Minority Health....S. Department of Health and Human Services and the Association of Minority Health Profession...

Since 2000 researchers have reported a decline in the administration of attention-deficit/hyperactivity disorder (ADHD) medications given by school nurses, although no decline has been noted in the incidence of ADHD in school-age populations. Government data for the same period show reduced levels of methylphenidate abuse as measured by its…

... Administration (FDA) is correcting a notice that appeared in the Federal Register of July 6, 2012 (77 FR 40069... Spring, MD 20993-0002, 301- 796-3485, astrid.lopezgoldberg@fda.hhs.gov . SUPPLEMENTARY INFORMATION: In FR... are labeled for human use, and persons who manufacture or cause the manufacture or distribution...

Our previous studies demonstrated feasibility of magnetically-mediated retention of iron-oxide nanoparticles in brain tumors after intravascular administration. The purpose of this study was to elucidate strategies for further improvement of this promising approach. In particular, we explored administration of the nanoparticles via a non-occluded carotid artery as a way to increase the passive exposure of tumor vasculature to nanoparticles for subsequent magnetic entrapment. However, aggregation of nanoparticles in the afferent vasculature interfered with tumor targeting. The magnetic setup employed in our experiments was found to generate a relatively uniform magnetic flux density over a broad range, exposing the region of the afferent vasculature to high magnetic force. To overcome this problem, the magnetic setup was modified with a 9-mm diameter cylindrical NdFeB magnet to exhibit steeper magnetic field topography. Six-fold reduction of the magnetic force at the injection site, achieved with this modification, alleviated the aggregation problem under the conditions of intact carotid blood flow. Using this setup, carotid administration was found to present 1.8-fold increase in nanoparticle accumulation in glioma compared to the intravenous route at 350 mT. This increase was found to be in reasonable agreement with the theoretically estimated 1.9-fold advantage of carotid administration, Rd. The developed approach is expected to present an even greater advantage when applied to drug-loaded nanoparticles exhibiting higher values of Rd. PMID:21763736

The Food and DrugAdministration (FDA) is publishing an order granting a petition requesting exemption from the premarket notification requirements for barium enema retention catheters and tips with or without a bag with certain limitations. This rule will exempt from premarket notification barium enema retention catheters and tips with or without a bag. FDA is publishing this order in accordance with procedures established by the Food and DrugAdministration Modernization Act of 1997 (FDAMA). PMID:11503724

This study in six cows compared serum concentrations of trimethoprim and sulphadoxine (16 mg/kg body weight (BW)) after once daily and twice daily administration, and of procaine penicillin G (20,000 IU/kg BW) after subcutaneous (SQ) and intramuscular (IM) administration, and evaluated postmortem tissue concentrations of penicillin following SQ treatment. Trimethoprim and penicillin were measured microbiologically, and sulphadoxine colorimetrically. Using minimum inhibitory concentrations (MIC), trimethoprim reached serum concentrations above 0.5 μg/mL from 15 minutes to 120 minutes, and sulphadoxine exceeded 9.5 μg/mL from 10 minutes to 12 hours, after administration. At 24 hours after treatment, both had declined to below the MIC of most organisms. A second treatment at 12 hours maintained concentrations of sulphadoxine above 9.5 μg/mL for a further 24 hours. For penicillin administered IM and SQ, concentrations that peaked at 0.88 μg/mL would inhibit most common grampositive bacteria for the entire 24 hour period and fastidious gram-negative organisms from 90 minutes to 12 hours after SQ treatment, but for virtually the entire period after IM administration. Mean ± SD concentrations (μg/mL) of penicillin at euthanasia, five days after the last SQ administration, were 1.15 ± 1.27 (injection site), 1.00 ± 0.80 (liver), 0.90 ± 0.58 (renal cortex), 0,58 ± 0.17 (renal medulla), 0.13 ± 0.11 (diaphragm), 0.10 ± 0.08 (gluteal muscle), and 0.06 ± 0.04 (fat). Therefore, except for the most sensitive organisms, twice daily injection of trimethoprim/sulphadoxine (16 mg/kg BW) may be required. Penicillin G administered SQ at 20,000 IU/kg BW should provide effective serum levels for as long as IM administration against gram-positive organisms, but for only about half as long against gram-negative bacteria. The label withdrawal time of five days cannot be used when penicillin is given SQ at 20,000 IU/kg BW for three days. PMID:17424305

Relative reinforcing effects of different ethanol and different cocaine doses were studied under concurrent independent fixed-ratio (FR) schedules and concurrent nonindependent FR schedules with rhesus monkeys. Nonindependent FR schedules differed from independent FR schedules in that responses on either side counted towards the FR requirements of two concurrently presented choices. Thus, responses on the right operandum counted toward completion of both right and left FR schedules and, symmetrically, responses on the left did the same. Nonindependent schedules allow the number of responses per drug delivery to vary considerably, unlike independent schedules, thereby making the number of responses per delivery a sensitive dependent variable. In contrast, standard independent schedules do not allow responses per drug delivery to vary; the required number of responses is an independent variable. Three rhesus monkeys were subjects, and choices between different doses of ethanol or cocaine were studied. Larger doses maintained higher response rates than smaller doses - consistent with previous choice studies. By using nonindependent schedules, however, graded responses per drug delivery and increased switching between sides were obtained, providing additional data and useful measures of choice. PMID:23549451

The present paper focuses on solid lipid particles (SLPs), described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL)-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero-order kinetics, which characterizes prolonged-release drug systems. PMID:27367664